Variant 7-143719925-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 1P and 0B. PP3

The NM_001363538.2(TCAF2):c.866C>T(p.Ala289Val) variant causes a missense change. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00035 ( 0 hom., cov: 15)

Exomes 𝑓: 0.000069 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

TCAF2
NM_001363538.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.04

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 Uncertain_significance. Variant got 1 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.772

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TCAF2	NM_001363538.2 linkuse as main transcript	c.866C>T	p.Ala289Val	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.866C>T	p.Ala289Val	missense_variant	3/8		NM_001363538.2	ENSP00000506869.1		A6NFQ2-1

Frequencies

GnomAD3 genomes

AF:

0.000349

AC:

AN:

117628

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00111

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000177

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000540

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000867

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000690

AC:

AN:

1290602

Hom.:

Cov.:

AF XY:

0.0000634

AC XY:

AN XY:

646544

show subpopulations

Gnomad4 AFR exome

AF:

0.00115

Gnomad4 AMR exome

AF:

0.0000251

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000325

Gnomad4 SAS exome

AF:

0.0000377

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000349

Gnomad4 OTH exome

AF:

0.000110

GnomAD4 genome

AF:

0.000348

AC:

AN:

117668

Hom.:

Cov.:

AF XY:

0.000268

AC XY:

AN XY:

56010

show subpopulations

Gnomad4 AFR

AF:

0.00111

Gnomad4 AMR

AF:

0.000177

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000543

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000867

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00118

Hom.:

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

Oct 21, 2021

The c.866C>T (p.A289V) 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 866, causing the alanine (A) at amino acid position 289 to be replaced by a valine (V). 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

0.23

BayesDel_addAF

Benign

-0.076

BayesDel_noAF

Benign

-0.35

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.24

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

Eigen

Uncertain

0.51

Eigen_PC

Uncertain

0.40

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.96

D;.;.;D;.;D;D

M_CAP

Benign

0.026

MetaRNN

Pathogenic

0.77

D;D;D;D;D;D;D

MetaSVM

Benign

-1.0

PrimateAI

Uncertain

0.71

PROVEAN

Uncertain

-3.3

D;D;.;D;D;.;.

REVEL

Benign

0.19

Sift

Uncertain

0.0030

D;D;.;D;T;.;.

Sift4G

Uncertain

0.041

D;D;.;D;T;T;.

Polyphen

1.0

D;D;D;D;D;D;D

Vest4

0.55

MutPred

0.47

Gain of MoRF binding (P = 0.1115);Gain of MoRF binding (P = 0.1115);Gain of MoRF binding (P = 0.1115);Gain of MoRF binding (P = 0.1115);.;.;.;

MVP

0.076

ClinPred

0.99

GERP RS

3.4

Varity_R

0.38

gMVP

0.76

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