rs73276080

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_017775.4(TTC19):c.-15G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00618 in 1,533,502 control chromosomes in the GnomAD database, including 482 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.032 ( 267 hom., cov: 32)

Exomes 𝑓: 0.0033 ( 215 hom. )

Consequence

TTC19
NM_017775.4 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.824

Publications

3 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 -18 ACMG points.

BP4

Computational evidence support a benign effect (REVEL=0.044).

BP6

Variant 17-15999834-G-A is Benign according to our data. Variant chr17-15999834-G-A is described in ClinVar as Benign. ClinVar VariationId is 137772.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.109 is higher than 0.05.

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	Effect	Exon Rank	Protein	UniProt
TTC19	NM_017775.4	MANE Select	c.-15G>A	5_prime_UTR	Exon 1 of 10	NP_060245.3
TTC19	NM_001271420.2		c.-473G>A	5_prime_UTR	Exon 1 of 10	NP_001258349.1
ZSWIM7	NM_001042697.2	MANE Select	c.-240C>T	upstream_gene	N/A	NP_001036162.1	Q19AV6

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TTC19	ENST00000261647.10	TSL:1 MANE Select	c.-15G>A	5_prime_UTR	Exon 1 of 10	ENSP00000261647.5	Q6DKK2
TTC19	ENST00000873205.1		c.-15G>A	5_prime_UTR	Exon 1 of 10	ENSP00000543264.1
TTC19	ENST00000873204.1		c.-15G>A	5_prime_UTR	Exon 1 of 10	ENSP00000543263.1

Frequencies

GnomAD3 genomes

AF:

0.0321

AC:

4883

AN:

152154

Hom.:

263

Cov.:

show subpopulations

Gnomad AFR

AF:

0.111

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0120

Gnomad ASJ

AF:

0.000289

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000827

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000412

Gnomad OTH

AF:

0.0229

GnomAD2 exomes

AF:

0.00611

AC:

805

AN:

131690

AF XY:

0.00464

show subpopulations

Gnomad AFR exome

AF:

0.128

Gnomad AMR exome

AF:

0.00596

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000617

Gnomad OTH exome

AF:

0.00492

GnomAD4 exome

AF:

0.00331

AC:

4572

AN:

1381236

Hom.:

215

Cov.:

AF XY:

0.00287

AC XY:

1957

AN XY:

682494

show subpopulations

African (AFR)

AF:

0.118

AC:

3542

AN:

29954

American (AMR)

AF:

0.00690

AC:

246

AN:

35664

Ashkenazi Jewish (ASJ)

AF:

0.0000408

AC:

AN:

24494

East Asian (EAS)

AF:

0.00

AC:

AN:

35376

South Asian (SAS)

AF:

0.000178

AC:

AN:

78768

European-Finnish (FIN)

AF:

0.00

AC:

AN:

34476

Middle Eastern (MID)

AF:

0.00574

AC:

AN:

4702

European-Non Finnish (NFE)

AF:

0.000219

AC:

237

AN:

1080230

Other (OTH)

AF:

0.00877

AC:

505

AN:

57572

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

201

401

602

802

1003

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

122

244

366

488

610

<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:

0.0322

AC:

4905

AN:

152266

Hom.:

267

Cov.:

AF XY:

0.0307

AC XY:

2284

AN XY:

74456

show subpopulations

African (AFR)

AF:

0.112

AC:

4641

AN:

41574

American (AMR)

AF:

0.0120

AC:

184

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.000289

AC:

AN:

3462

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.000621

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10600

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.000412

AC:

AN:

67996

Other (OTH)

AF:

0.0227

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

235

470

706

941

1176

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

144

192

240

<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:

0.0159

Hom.:

Bravo

AF:

0.0369

Asia WGS

AF:

0.00521

AC:

AN:

3468

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (2)

Mitochondrial complex III deficiency nuclear type 2 (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.20

CADD

Benign

(source)

DANN

Uncertain

1.0

PhyloP100

0.82

PromoterAI

-0.011

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

Mutation Taster

=284/16

polymorphism (auto)

(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