chr7-143859122-T-A

Variant names:

• chr7-143859122-T-A
• NM_014719.3:c.2207A>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014719.3(TCAF1):​c.2207A>T​(p.Glu736Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 23)
• Consequence: TCAF1 NM_014719.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.96
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.25943518).

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.2207A>T	p.Glu736Val	missense	Exon 7 of 9	NP_055534.2	Q9Y4C2-1
	TCAF1	NM_001206938.2		c.2207A>T	p.Glu736Val	missense	Exon 7 of 9	NP_001193867.2	Q9Y4C2-2
	TCAF1	NM_001206941.2		c.935A>T	p.Glu312Val	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.2207A>T	p.Glu736Val	missense	Exon 7 of 9	ENSP00000419235.1	Q9Y4C2-1
	TCAF1	ENST00000355951.2	TSL:1	c.2207A>T	p.Glu736Val	missense	Exon 7 of 9	ENSP00000348220.2	Q9Y4C2-2
	TCAF1	ENST00000872784.1		c.2207A>T	p.Glu736Val	missense	Exon 7 of 9	ENSP00000542843.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 27

GnomAD4 genome Cov.: 23

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	0.45
BayesDel_addAF	Uncertain	0.16	D
BayesDel_noAF	Uncertain	-0.010
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Benign	0.094	T
Eigen	Uncertain	0.28
Eigen_PC	Benign	0.19
FATHMM_MKL	Benign	0.54	D
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.0076	T
MetaRNN	Benign	0.26	T
MetaSVM	Benign	-0.75	T
PhyloP100		2.0
PrimateAI	Uncertain	0.61	T
PROVEAN	Uncertain	-3.6	D
REVEL	Uncertain	0.37
Sift	Benign	0.034	D
Sift4G	Benign	0.20	T
Polyphen		0.83	P
Vest4		0.32
MutPred		0.57		Loss of solvent accessibility (P = 0.0224)
MVP		0.21
MPC		3.5
ClinPred		0.98	D
GERP RS		3.2
Varity_R		0.29
gMVP		0.52
Mutation Taster		=86/14	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

hg19: chr7-143556215;