Variant chr7-143703230-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001363538.2(TCAF2):c.236T>C(p.Leu79Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 5)

Exomes 𝑓: 0.0 ( 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: -0.116

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.

BP4

Computational evidence support a benign effect (MetaRNN=0.18822986).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TCAF2	NM_001363538.2 linkuse as main transcript	c.236T>C	p.Leu79Pro	missense_variant	2/8	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.236T>C	p.Leu79Pro	missense_variant	2/8		NM_001363538.2	ENSP00000506869	P1	A6NFQ2-1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

56222

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

1423950

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

709334

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

56222

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

27424

Gnomad4 AFR

AF:

0.00

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:

0.00

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

Aug 02, 2021

The c.236T>C (p.L79P) alteration is located in exon 2 (coding exon 1) of the TCAF2 gene. This alteration results from a T to C substitution at nucleotide position 236, causing the leucine (L) at amino acid position 79 to be replaced by a proline (P). 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

Uncertain

0.41

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.41

CADD

Benign

8.5

DANN

Benign

0.95

DEOGEN2

Benign

0.12

.;.;.;T

Eigen

Benign

-0.61

Eigen_PC

Benign

-0.91

FATHMM_MKL

Benign

0.059

LIST_S2

Benign

0.84

T;.;.;T

M_CAP

Benign

0.0038

MetaRNN

Benign

0.19

T;T;T;T

MetaSVM

Benign

-1.1

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Benign

0.39

PROVEAN

Benign

-1.1

N;N;.;N

REVEL

Benign

0.13

Sift

Benign

0.12

T;T;.;T

Sift4G

Benign

0.27

T;T;.;T

Polyphen

0.90

P;P;P;.

Vest4

0.52

MutPred

0.39

Loss of stability (P = 0.0475);Loss of stability (P = 0.0475);Loss of stability (P = 0.0475);Loss of stability (P = 0.0475);

MVP

0.076

ClinPred

0.21

GERP RS

-7.5

Varity_R

0.13

gMVP

0.78

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over