Variant 7-143720003-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001363538.2(TCAF2):c.944C>T(p.Ser315Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000892 in 145,782 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000089 ( 0 hom., cov: 23)

Exomes 𝑓: 0.000053 ( 1 hom. )

Failed GnomAD Quality Control

Consequence

TCAF2
NM_001363538.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.274

Variant links:

Genes affected

TCAF2 (HGNC:26878): (TRPM8 channel associated factor 2) Enables transmembrane transporter binding activity. Involved in negative regulation of anion channel activity; positive regulation of cell migration; and positive regulation of protein targeting to membrane. Located in cell junction and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

TCAF2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06238669).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TCAF2	NM_001363538.2 linkuse as main transcript	c.944C>T	p.Ser315Leu	missense_variant	3/8	ENST00000684770.1	NP_001350467.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TCAF2	ENST00000684770.1 linkuse as main transcript	c.944C>T	p.Ser315Leu	missense_variant	3/8		NM_001363538.2	ENSP00000506869	P1	A6NFQ2-1

Frequencies

GnomAD3 genomes

AF:

0.0000892

AC:

AN:

145684

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000532

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000136

Gnomad ASJ

AF:

0.000298

Gnomad EAS

AF:

0.000200

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000105

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000392

AC:

AN:

204330

Hom.:

AF XY:

0.0000180

AC XY:

AN XY:

111098

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000100

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000551

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000531

AC:

AN:

1432302

Hom.:

Cov.:

AF XY:

0.0000616

AC XY:

AN XY:

713868

show subpopulations

Gnomad4 AFR exome

AF:

0.000127

Gnomad4 AMR exome

AF:

0.000135

Gnomad4 ASJ exome

AF:

0.000349

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000505

Gnomad4 OTH exome

AF:

0.0000338

GnomAD4 genome

AF:

0.0000892

AC:

AN:

145782

Hom.:

Cov.:

AF XY:

0.0000703

AC XY:

AN XY:

71144

show subpopulations

Gnomad4 AFR

AF:

0.0000531

Gnomad4 AMR

AF:

0.000136

Gnomad4 ASJ

AF:

0.000298

Gnomad4 EAS

AF:

0.000201

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000105

Gnomad4 OTH

AF:

0.00

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

Mar 02, 2023

The c.944C>T (p.S315L) alteration is located in exon 3 (coding exon 2) of the TCAF2 gene. This alteration results from a C to T substitution at nucleotide position 944, causing the serine (S) at amino acid position 315 to be replaced by a leucine (L). 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

0.068

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.58

CADD

Benign

8.5

DANN

Benign

0.74

DEOGEN2

Benign

0.036

.;.;.;T;.;.;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.062

LIST_S2

Benign

0.59

T;.;.;T;.;T;T

M_CAP

Benign

0.0049

MetaRNN

Benign

0.062

T;T;T;T;T;T;T

MetaSVM

Benign

-0.97

MutationTaster

Benign

1.0

N;N;N;N;N;N;N

PrimateAI

Benign

0.31

PROVEAN

Benign

-2.0

N;N;.;N;N;.;.

REVEL

Benign

0.019

Sift

Benign

0.47

T;T;.;T;T;.;.

Sift4G

Benign

0.35

T;T;.;T;T;T;.

Polyphen

0.0090

B;B;B;B;B;B;B

Vest4

0.099

MutPred

0.26

Loss of disorder (P = 0.0532);Loss of disorder (P = 0.0532);Loss of disorder (P = 0.0532);Loss of disorder (P = 0.0532);.;.;.;

MVP

0.11

ClinPred

0.048

GERP RS

1.4

Varity_R

0.033

gMVP

0.46

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