rs746854510

Variant names:

• chr7-143876514-A-C
• NM_014719.3:c.95T>G

Your query was ambiguous. Multiple possible variants found:

• chr7-143876514-A-C
• chr7-143876514-A-G
• chr7-143876514-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014719.3(TCAF1):​c.95T>G​(p.Ile32Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000842 in 1,424,546 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000084 (0 hom.)
• Consequence: TCAF1 NM_014719.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.30

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.23413005).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TCAF1	NM_014719.3	c.95T>G	p.Ile32Ser	missense_variant	Exon 2 of 9	ENST00000479870.6	NP_055534.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TCAF1	ENST00000479870.6	c.95T>G	p.Ile32Ser	missense_variant	Exon 2 of 9	1	NM_014719.3	ENSP00000419235.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000842 AC: 12 AN: 1424546 Hom.: 0 Cov.: 32 AF XY: 0.00000850 AC XY: 6 AN XY: 706208

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: 0.0000109

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.013	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.11	T;.;T;.;T;.
Eigen	Benign	-0.12
Eigen_PC	Benign	-0.20
FATHMM_MKL	Benign	0.60	D
LIST_S2	Uncertain	0.94	D;D;.;D;D;D
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.23	T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-1.9	N;N;N;N;N;D
REVEL	Benign	0.17
Sift	Benign	0.077	T;T;D;D;D;T
Sift4G	Uncertain	0.034	D;D;T;T;.;T
Polyphen		0.69	P;.;.;.;.;.
Vest4		0.72
MutPred		0.53		Loss of stability (P = 0.0145);Loss of stability (P = 0.0145);Loss of stability (P = 0.0145);Loss of stability (P = 0.0145);Loss of stability (P = 0.0145);Loss of stability (P = 0.0145);
MVP		0.088
MPC		0.092
ClinPred		0.90	D
GERP RS		2.8
Varity_R		0.21
gMVP		0.82

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-143573607;