Variant 7-143858957-A-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_014719.3(TCAF1):c.2372T>G(p.Leu791Trp) variant causes a missense change involving the alteration of a conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 22)

Exomes 𝑓: 0.000048 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

TCAF1
NM_014719.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.90

Variant links:

Genes affected

TCAF1 (HGNC:22201): (TRPM8 channel associated factor 1) Enables transmembrane transporter binding activity. Involved in negative regulation of cell migration; positive regulation of anion channel activity; and positive regulation of protein targeting to membrane. Located in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

TCAF1 links:

LOC112267988 (HGNC:):

LOC112267988 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TCAF1	NM_014719.3 linkuse as main transcript	c.2372T>G	p.Leu791Trp	missense_variant	7/9	ENST00000479870.6	NP_055534.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TCAF1	ENST00000479870.6 linkuse as main transcript	c.2372T>G	p.Leu791Trp	missense_variant	7/9	1	NM_014719.3	ENSP00000419235	P4	Q9Y4C2-1
TCAF1	ENST00000355951.2 linkuse as main transcript	c.2372T>G	p.Leu791Trp	missense_variant	7/9	1		ENSP00000348220	A1	Q9Y4C2-2
TCAF1	ENST00000392900.3 linkuse as main transcript	n.1814T>G		non_coding_transcript_exon_variant	6/8	2

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

149120

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.0000251

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:

0.0000148

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000482

AC:

AN:

580744

Hom.:

Cov.:

AF XY:

0.0000483

AC XY:

AN XY:

310306

show subpopulations

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:

0.0000781

Gnomad4 OTH exome

AF:

0.0000650

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000134

AC:

AN:

149120

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

72660

show subpopulations

Gnomad4 AFR

AF:

0.0000251

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:

0.0000148

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

Jun 11, 2021

The c.2372T>G (p.L791W) alteration is located in exon 7 (coding exon 6) of the TCAF1 gene. This alteration results from a T to G substitution at nucleotide position 2372, causing the leucine (L) at amino acid position 791 to be replaced by a tryptophan (W). 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

0.56

BayesDel_addAF

Pathogenic

0.16

BayesDel_noAF

Uncertain

0.0

CADD

Pathogenic

DANN

Benign

0.96

DEOGEN2

Benign

0.19

T;.

Eigen

Pathogenic

0.75

Eigen_PC

Uncertain

0.62

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.95

D;D

M_CAP

Benign

0.023

MetaRNN

Uncertain

0.66

D;D

MetaSVM

Uncertain

-0.029

MutationTaster

Benign

0.98

D;D

PrimateAI

Pathogenic

0.82

PROVEAN

Pathogenic

-5.3

D;D

REVEL

Uncertain

0.64

Sift

Pathogenic

0.0

D;D

Sift4G

Pathogenic

0.0010

D;D

Polyphen

1.0

D;.

Vest4

0.56

MutPred

0.75

Gain of catalytic residue at P794 (P = 0.0265);Gain of catalytic residue at P794 (P = 0.0265);

MVP

0.25

MPC

5.0

ClinPred

0.97

GERP RS

3.2

Varity_R

0.81

gMVP

0.77

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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