Variant 7-143719762-C-G 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.703C>G(p.Pro235Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000072 ( 0 hom., cov: 17)

Exomes 𝑓: 0.000038 ( 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: 2.12

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, 0.749

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TCAF2	NM_001363538.2 linkuse as main transcript	c.703C>G	p.Pro235Ala	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.703C>G	p.Pro235Ala	missense_variant	3/8		NM_001363538.2	ENSP00000506869.1		A6NFQ2-1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

138062

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000733

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000376

AC:

AN:

584704

Hom.:

Cov.:

AF XY:

0.0000428

AC XY:

AN XY:

304040

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000308

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000298

Gnomad4 OTH exome

AF:

0.0000991

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000724

AC:

AN:

138062

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

66612

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000733

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

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

Feb 01, 2023

The c.703C>G (p.P235A) alteration is located in exon 3 (coding exon 2) of the TCAF2 gene. This alteration results from a C to G substitution at nucleotide position 703, causing the proline (P) at amino acid position 235 to be replaced by an alanine (A). 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

0.21

BayesDel_addAF

Uncertain

0.022

BayesDel_noAF

Benign

-0.21

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.16

.;.;.;T;.;.

Eigen

Benign

0.044

Eigen_PC

Benign

-0.019

FATHMM_MKL

Uncertain

0.81

LIST_S2

Uncertain

0.86

D;.;.;D;.;D

M_CAP

Benign

0.040

MetaRNN

Pathogenic

0.75

D;D;D;D;D;D

MetaSVM

Benign

-0.50

PrimateAI

Uncertain

0.58

PROVEAN

Pathogenic

-4.9

D;D;.;D;D;.

REVEL

Uncertain

0.45

Sift

Uncertain

0.014

D;D;.;D;T;.

Sift4G

Benign

0.35

T;T;.;T;T;T

Polyphen

1.0

D;D;D;D;D;D

Vest4

0.32

MutPred

0.64

Gain of catalytic residue at P235 (P = 0.1862);Gain of catalytic residue at P235 (P = 0.1862);Gain of catalytic residue at P235 (P = 0.1862);Gain of catalytic residue at P235 (P = 0.1862);.;.;

MVP

0.13

ClinPred

0.99

GERP RS

2.6

Varity_R

0.33

gMVP

0.67

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