7-143857296-T-C

Variant names:

• chr7-143857296-T-C
• rs1378718673
• NM_014719.3:c.2560A>G

Variant summary

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

The NM_014719.3(TCAF1):​c.2560A>G​(p.Asn854Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000067 (0 hom., cov: 22)
  • Exomes 𝑓: 0.0000073 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TCAF1 NM_014719.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.980
• 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]

ENSG00000309129 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.10598126).

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.2560A>G	p.Asn854Asp	missense	Exon 8 of 9	NP_055534.2	Q9Y4C2-1
	TCAF1	NM_001206938.2		c.2560A>G	p.Asn854Asp	missense	Exon 8 of 9	NP_001193867.2	Q9Y4C2-2
	TCAF1	NM_001206941.2		c.1288A>G	p.Asn430Asp	missense	Exon 7 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.2560A>G	p.Asn854Asp	missense	Exon 8 of 9	ENSP00000419235.1	Q9Y4C2-1
	TCAF1	ENST00000355951.2	TSL:1	c.2560A>G	p.Asn854Asp	missense	Exon 8 of 9	ENSP00000348220.2	Q9Y4C2-2
	TCAF1	ENST00000872784.1		c.2560A>G	p.Asn854Asp	missense	Exon 8 of 9	ENSP00000542843.1

Frequencies

GnomAD3 genomes AF: 0.00000667 AC: 1 AN: 149972 Hom.: 0 Cov.: 22

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000668

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

GnomAD2 exomes AF: 0.0000191 AC: 2 AN: 104620 AF XY: 0.0000185

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000136

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 Data not reliable, filtered out with message: AS_VQSR AF: 0.00000733 AC: 6 AN: 818572 Hom.: 0 Cov.: 11 AF XY: 0.00000704 AC XY: 3 AN XY: 426410

⚠️ 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: 20414

American (AMR) AF: 0.000150 AC: 5 AN: 33226

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19912

East Asian (EAS) AF: 0.00 AC: 0 AN: 36162

South Asian (SAS) AF: 0.00 AC: 0 AN: 67222

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50316

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3000

European-Non Finnish (NFE) AF: 0.00000182 AC: 1 AN: 549414

Other (OTH) AF: 0.00 AC: 0 AN: 38906

⚠️ 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: 0.00000667 AC: 1 AN: 149972 Hom.: 0 Cov.: 22 AF XY: 0.0000137 AC XY: 1 AN XY: 73084

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

African (AFR) AF: 0.00 AC: 0 AN: 40244

American (AMR) AF: 0.0000668 AC: 1 AN: 14980

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3444

East Asian (EAS) AF: 0.00 AC: 0 AN: 5074

South Asian (SAS) AF: 0.00 AC: 0 AN: 4694

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10526

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 312

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67752

Other (OTH) AF: 0.00 AC: 0 AN: 2040

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), 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	Benign	0.089
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Uncertain	24
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0083	T
Eigen	Benign	-0.31
Eigen_PC	Benign	-0.16
FATHMM_MKL	Benign	0.74	D
LIST_S2	Benign	0.46	T
M_CAP	Benign	0.0019	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.1	T
PhyloP100		0.98
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	-0.82	N
REVEL	Benign	0.065
Sift	Benign	0.15	T
Sift4G	Benign	0.67	T
Polyphen		0.46	P
Vest4		0.13
MutPred		0.34		Gain of disorder (P = 0.1745)
MVP		0.081
MPC		2.2
ClinPred		0.13	T
GERP RS		3.7
Varity_R		0.13
gMVP		0.18
Mutation Taster		=96/4	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: rs1378718673; hg19: chr7-143554389;