NM_014719.3:c.2372T>G

Variant names:

• chr7-143858957-A-C
• rs1296845188
• NM_014719.3:c.2372T>G

Variant summary

Our verdict is Uncertain significance. The variant received 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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.90
• Publications: 1 publications found

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]

ENSG00000309129 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014719.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TCAF1	NM_014719.3	MANE Select	c.2372T>G	p.Leu791Trp	missense	Exon 7 of 9	NP_055534.2	Q9Y4C2-1
	TCAF1	NM_001206938.2		c.2372T>G	p.Leu791Trp	missense	Exon 7 of 9	NP_001193867.2	Q9Y4C2-2
	TCAF1	NM_001206941.2		c.1100T>G	p.Leu367Trp	missense	Exon 6 of 8	NP_001193870.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TCAF1	ENST00000479870.6	TSL:1 MANE Select	c.2372T>G	p.Leu791Trp	missense	Exon 7 of 9	ENSP00000419235.1	Q9Y4C2-1
	TCAF1	ENST00000355951.2	TSL:1	c.2372T>G	p.Leu791Trp	missense	Exon 7 of 9	ENSP00000348220.2	Q9Y4C2-2
	TCAF1	ENST00000872784.1		c.2372T>G	p.Leu791Trp	missense	Exon 7 of 9	ENSP00000542843.1

Frequencies

GnomAD3 genomes AF: 0.0000134 AC: 2 AN: 149120 Hom.: 0 Cov.: 22

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

GnomAD2 exomes AF: 0.0000172 AC: 2 AN: 116230 AF XY: 0.0000327

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000454

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000482 AC: 28 AN: 580744 Hom.: 0 Cov.: 6 AF XY: 0.0000483 AC XY: 15 AN XY: 310306

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 16130

American (AMR) AF: 0.00 AC: 0 AN: 34020

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19008

East Asian (EAS) AF: 0.00 AC: 0 AN: 32918

South Asian (SAS) AF: 0.00 AC: 0 AN: 63140

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49568

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2414

European-Non Finnish (NFE) AF: 0.0000781 AC: 26 AN: 332778

Other (OTH) AF: 0.0000650 AC: 2 AN: 30768

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000134 AC: 2 AN: 149120 Hom.: 0 Cov.: 22 AF XY: 0.00 AC XY: 0 AN XY: 72660

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000251 AC: 1 AN: 39834

American (AMR) AF: 0.00 AC: 0 AN: 14894

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3446

East Asian (EAS) AF: 0.00 AC: 0 AN: 5070

South Asian (SAS) AF: 0.00 AC: 0 AN: 4608

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10486

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000148 AC: 1 AN: 67542

Other (OTH) AF: 0.00 AC: 0 AN: 2018

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.0000812204), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.56
BayesDel_addAF	Pathogenic	0.16	D
BayesDel_noAF	Uncertain	0.0
CADD	Pathogenic	29
DANN	Benign	0.96
DEOGEN2	Benign	0.19	T
Eigen	Pathogenic	0.75
Eigen_PC	Uncertain	0.62
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.023	T
MetaRNN	Uncertain	0.66	D
MetaSVM	Uncertain	-0.029	T
PhyloP100		8.9
PrimateAI	Pathogenic	0.82	D
PROVEAN	Pathogenic	-5.3	D
REVEL	Uncertain	0.64
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0010	D
Polyphen		1.0	D
Vest4		0.56
MutPred		0.75		Gain of catalytic residue at P794 (P = 0.0265)
MVP		0.25
MPC		5.0
ClinPred		0.97	D
GERP RS		3.2
Varity_R		0.81
gMVP		0.77
Mutation Taster		=55/45	polymorphism

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

Other links and lift over

dbSNP: rs1296845188; hg19: chr7-143556050;