dbSNP rs11623837: TTC5:c.1058+1405T>C (chr14-20293907-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_138376.3(TTC5):c.1058+1405T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.413 in 152,030 control chromosomes in the GnomAD database, including 13,129 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.41 ( 13129 hom., cov: 32)

Exomes 𝑓: 0.19 ( 0 hom. )

Consequence

TTC5
NM_138376.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.113

Publications

6 publications found

Variant links:

Genes affected

TTC5 (HGNC:19274): (tetratricopeptide repeat domain 5) Predicted to enable DNA binding activity and chromatin binding activity. Predicted to be involved in DNA repair. Predicted to act upstream of or within positive regulation of transcription by RNA polymerase II. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

TTC5 Gene-Disease associations (from GenCC):

neurodevelopmental disorder with cerebral atrophy and variable facial dysmorphism
Inheritance: AR Classification: STRONG, LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
autosomal recessive non-syndromic intellectual disability
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

TTC5 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.443 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TTC5	NM_138376.3 link	c.1058+1405T>C		intron_variant	Intron 8 of 9	ENST00000258821.8	NP_612385.2	Q8N0Z6Q86T04

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
TTC5	ENST00000258821.8 link	c.1058+1405T>C	intron_variant	Intron 8 of 9	1	NM_138376.3	ENSP00000258821.3	Q8N0Z6
TTC5	ENST00000383029.7 link	n.*603+1405T>C	intron_variant	Intron 8 of 9	1		ENSP00000372496.3	H9KV81
TTC5	ENST00000554157.5 link	n.2474T>C	non_coding_transcript_exon_variant	Exon 8 of 9	2

Frequencies

GnomAD3 genomes

AF:

0.413

AC:

62763

AN:

151896

Hom.:

13132

Cov.:

show subpopulations

Gnomad AFR

AF:

0.449

Gnomad AMI

AF:

0.271

Gnomad AMR

AF:

0.331

Gnomad ASJ

AF:

0.416

Gnomad EAS

AF:

0.269

Gnomad SAS

AF:

0.337

Gnomad FIN

AF:

0.455

Gnomad MID

AF:

0.396

Gnomad NFE

AF:

0.422

Gnomad OTH

AF:

0.400

GnomAD4 exome

AF:

0.188

AC:

AN:

Hom.:

Cov.:

AF XY:

0.167

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.500

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.200

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.625

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.413

AC:

62782

AN:

152014

Hom.:

13129

Cov.:

AF XY:

0.410

AC XY:

30442

AN XY:

74332

show subpopulations

African (AFR)

AF:

0.448

AC:

18583

AN:

41434

American (AMR)

AF:

0.331

AC:

5048

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.416

AC:

1443

AN:

3472

East Asian (EAS)

AF:

0.269

AC:

1392

AN:

5174

South Asian (SAS)

AF:

0.336

AC:

1617

AN:

4812

European-Finnish (FIN)

AF:

0.455

AC:

4809

AN:

10566

Middle Eastern (MID)

AF:

0.384

AC:

113

AN:

294

European-Non Finnish (NFE)

AF:

0.422

AC:

28694

AN:

67972

Other (OTH)

AF:

0.396

AC:

836

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1904

3807

5711

7614

9518

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

592

1184

1776

2368

2960

<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:

0.412

Hom.:

2468

Bravo

AF:

0.407

Asia WGS

AF:

0.312

AC:

1084

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

2.4

(source)

DANN

Benign

0.84

PhyloP100

0.11

Mutation Taster

=100/0

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over