7-143876605-C-A

Variant names:

• chr7-143876605-C-A
• rs980011806
• NM_014719.3:c.4G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_014719.3(TCAF1):​c.4G>T​(p.Ala2Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000864 in 1,504,538 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A2V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000053 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000037 (0 hom.)
• Consequence: TCAF1 NM_014719.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.474
• Publications: 0 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]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.1792661).

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.4G>T	p.Ala2Ser	missense	Exon 2 of 9	NP_055534.2	Q9Y4C2-1
	TCAF1	NM_001206938.2		c.4G>T	p.Ala2Ser	missense	Exon 2 of 9	NP_001193867.2	Q9Y4C2-2
	TCAF1	NM_001206941.2		c.-653+8605G>T		intron	N/A	NP_001193870.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TCAF1	ENST00000479870.6	TSL:1 MANE Select	c.4G>T	p.Ala2Ser	missense	Exon 2 of 9	ENSP00000419235.1	Q9Y4C2-1
	TCAF1	ENST00000355951.2	TSL:1	c.4G>T	p.Ala2Ser	missense	Exon 2 of 9	ENSP00000348220.2	Q9Y4C2-2
	TCAF1	ENST00000872784.1		c.4G>T	p.Ala2Ser	missense	Exon 2 of 9	ENSP00000542843.1

Frequencies

GnomAD3 genomes AF: 0.0000526 AC: 8 AN: 152218 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000458

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: 0.000478

GnomAD2 exomes AF: 0.00000571 AC: 1 AN: 175086 AF XY: 0.0000109

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000497

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000370 AC: 5 AN: 1352320 Hom.: 0 Cov.: 31 AF XY: 0.00000605 AC XY: 4 AN XY: 660896

African (AFR) AF: 0.00 AC: 0 AN: 30098

American (AMR) AF: 0.000141 AC: 4 AN: 28446

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19646

East Asian (EAS) AF: 0.00 AC: 0 AN: 38714

South Asian (SAS) AF: 0.00 AC: 0 AN: 63686

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49440

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5278

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1061318

Other (OTH) AF: 0.0000180 AC: 1 AN: 55694

GnomAD4 genome AF: 0.0000526 AC: 8 AN: 152218 Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3 AN XY: 74364

African (AFR) AF: 0.00 AC: 0 AN: 41450

American (AMR) AF: 0.000458 AC: 7 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5200

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68036

Other (OTH) AF: 0.000478 AC: 1 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000907

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	Benign	0.081
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0053	T
Eigen	Benign	-0.29
Eigen_PC	Benign	-0.17
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.0032	T
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-0.98	T
PhyloP100		0.47
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	0.070	N
REVEL	Benign	0.055
Sift	Benign	0.071	T
Sift4G	Benign	0.10	T
Polyphen		0.30	B
Vest4		0.14
MutPred		0.12		Gain of glycosylation at A2 (P = 0.0049)
MVP		0.081
MPC		0.048
ClinPred		0.29	T
GERP RS		4.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.066
gMVP		0.51
Mutation Taster		=80/20	polymorphism

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

Other links and lift over

dbSNP: rs980011806; hg19: chr7-143573698;