Variant chr22-46274041-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The ENST00000381031.8(TTC38):c.337G>A(p.Val113Met) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000341 in 1,613,950 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000099 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000027 ( 0 hom. )

Consequence

TTC38
ENST00000381031.8 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.28

Variant links:

Genes affected

TTC38 (HGNC:26082): (tetratricopeptide repeat domain 38) Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

TTC38 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TTC38	NM_017931.4 linkuse as main transcript	c.337G>A	p.Val113Met	missense_variant	4/14	ENST00000381031.8	NP_060401.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
TTC38	ENST00000381031.8 linkuse as main transcript	c.337G>A	p.Val113Met	missense_variant	4/14	1	NM_017931.4	ENSP00000370419	P1
TTC38	ENST00000421359.5 linkuse as main transcript	c.337G>A	p.Val113Met	missense_variant	4/7	4		ENSP00000410095
TTC38	ENST00000422713.1 linkuse as main transcript	c.190G>A	p.Val64Met	missense_variant, NMD_transcript_variant	2/7	5		ENSP00000406604
TTC38	ENST00000417709.5 linkuse as main transcript	c.*323G>A		3_prime_UTR_variant, NMD_transcript_variant	5/6	3		ENSP00000391236

Frequencies

GnomAD3 genomes

AF:

0.0000986

AC:

AN:

152180

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000217

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.0000843

AC:

AN:

249202

Hom.:

AF XY:

0.000118

AC XY:

AN XY:

135270

show subpopulations

Gnomad AFR exome

AF:

0.000129

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000142

Gnomad OTH exome

AF:

0.000165

GnomAD4 exome

AF:

0.0000274

AC:

AN:

1461770

Hom.:

Cov.:

AF XY:

0.0000330

AC XY:

AN XY:

727178

show subpopulations

Gnomad4 AFR exome

AF:

0.000149

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000279

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

AF:

0.0000986

AC:

AN:

152180

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

74340

show subpopulations

Gnomad4 AFR

AF:

0.000217

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.0000966

Hom.:

Bravo

AF:

0.000174

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000119

AC:

ExAC

AF:

0.000116

AC:

EpiCase

AF:

0.000491

EpiControl

AF:

0.000533

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 23, 2023

The c.337G>A (p.V113M) alteration is located in exon 4 (coding exon 4) of the TTC38 gene. This alteration results from a G to A substitution at nucleotide position 337, causing the valine (V) at amino acid position 113 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.33

BayesDel_addAF

Uncertain

0.026

BayesDel_noAF

Uncertain

0.040

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.016

T;.

Eigen

Pathogenic

0.90

Eigen_PC

Pathogenic

0.86

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Uncertain

0.95

D;D

M_CAP

Uncertain

0.14

MetaRNN

Uncertain

0.54

D;D

MetaSVM

Uncertain

-0.0031

MutationAssessor

Pathogenic

3.0

M;.

MutationTaster

Benign

1.0

D;N

PrimateAI

Uncertain

0.56

PROVEAN

Benign

-1.9

N;N

REVEL

Uncertain

0.33

Sift

Uncertain

0.0040

D;D

Sift4G

Uncertain

0.0060

D;D

Polyphen

1.0

D;.

Vest4

0.76

MVP

0.59

MPC

0.78

ClinPred

0.46

GERP RS

5.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.33

gMVP

0.58

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over