dbSNP rs781647443: TTC19:p.Leu9Leu (chr17-15999875-G-C) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_017775.4(TTC19):c.27G>C(p.Leu9Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000549 in 1,439,172 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. L9L) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000056 ( 2 hom. )

Consequence

TTC19
NM_017775.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.00400

Publications

0 publications found

Variant links:

Genes affected

TTC19 (HGNC:26006): (tetratricopeptide repeat domain 19) This gene encodes a protein with a tetratricopeptide repeat (TPR) domain containing several TPRs of about 34 aa each. These repeats are found in a variety of organisms including bacteria, fungi and plants, and are involved in a variety of functions including protein-protein interactions. This protein is embedded in the inner mitochondrial membrane and is involved in the formation of the mitochondrial respiratory chain III. It has also been suggested that this protein plays a role in cytokinesis. Mutations in this gene cause mitochondrial complex III deficiency. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Sep 2012]

TTC19 links:

ZSWIM7 (HGNC:26993): (zinc finger SWIM-type containing 7) Predicted to enable zinc ion binding activity. Involved in double-strand break repair via homologous recombination and protein stabilization. Part of Shu complex. [provided by Alliance of Genome Resources, Apr 2022]

ZSWIM7 Gene-Disease associations (from GenCC):

male infertility with azoospermia or oligozoospermia due to single gene mutation
Inheritance: AR Classification: STRONG Submitted by: King Faisal Specialist Hospital and Research Center
ovarian dysgenesis 10
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
colorectal adenoma
Inheritance: Unknown Classification: LIMITED Submitted by: Ambry Genetics

ZSWIM7 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 17-15999875-G-C is Benign according to our data. Variant chr17-15999875-G-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 378796.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.004 with no splicing effect.

BS1

Variant frequency is greater than expected in population sas. GnomAdExome4 allele frequency = 0.0000559 (72/1286988) while in subpopulation SAS AF = 0.00108 (71/65578). AF 95% confidence interval is 0.00088. There are 2 homozygotes in GnomAdExome4. There are 55 alleles in the male GnomAdExome4 subpopulation. Median coverage is 30. This position passed quality control check.

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017775.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TTC19	NM_017775.4	MANE Select	c.27G>C	p.Leu9Leu	synonymous	Exon 1 of 10	NP_060245.3
TTC19	NM_001271420.2		c.-432G>C		5_prime_UTR	Exon 1 of 10	NP_001258349.1
ZSWIM7	NM_001042697.2	MANE Select	c.-281C>G		upstream_gene	N/A	NP_001036162.1	Q19AV6

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TTC19	ENST00000261647.10	TSL:1 MANE Select	c.27G>C	p.Leu9Leu	synonymous	Exon 1 of 10	ENSP00000261647.5	Q6DKK2
TTC19	ENST00000873205.1		c.27G>C	p.Leu9Leu	synonymous	Exon 1 of 10	ENSP00000543264.1
TTC19	ENST00000873204.1		c.27G>C	p.Leu9Leu	synonymous	Exon 1 of 10	ENSP00000543263.1

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152074

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000620

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00955

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.000373

AC:

AN:

48206

AF XY:

0.000509

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000559

AC:

AN:

1286988

Hom.:

Cov.:

AF XY:

0.0000874

AC XY:

AN XY:

628978

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

25536

American (AMR)

AF:

0.00

AC:

AN:

20316

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19976

East Asian (EAS)

AF:

0.00

AC:

AN:

30228

South Asian (SAS)

AF:

0.00108

AC:

AN:

65578

European-Finnish (FIN)

AF:

0.00

AC:

AN:

31252

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3798

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1037054

Other (OTH)

AF:

0.0000188

AC:

AN:

53250

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.449

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000460

AC:

AN:

152184

Hom.:

Cov.:

AF XY:

0.0000672

AC XY:

AN XY:

74410

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41566

American (AMR)

AF:

0.00

AC:

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5170

South Asian (SAS)

AF:

0.000621

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10568

Middle Eastern (MID)

AF:

0.0103

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67968

Other (OTH)

AF:

0.000473

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000936

Hom.:

Bravo

AF:

0.00000756

Asia WGS

AF:

0.000580

AC:

AN:

3464

ClinVar

ClinVar submissions as Germline

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

3.6

(source)

DANN

Benign

0.60

PhyloP100

-0.0040

PromoterAI

-0.10

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over