7-143876514-A-T

Variant names:

• chr7-143876514-A-T
• rs746854510
• NM_014719.3:c.95T>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_014719.3(TCAF1):​c.95T>A​(p.Ile32Asn) 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. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I32T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TCAF1 NM_014719.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.30
• 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.26750135).

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.95T>A	p.Ile32Asn	missense	Exon 2 of 9	NP_055534.2	Q9Y4C2-1
	TCAF1	NM_001206938.2		c.95T>A	p.Ile32Asn	missense	Exon 2 of 9	NP_001193867.2	Q9Y4C2-2
	TCAF1	NM_001206941.2		c.-653+8696T>A		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.95T>A	p.Ile32Asn	missense	Exon 2 of 9	ENSP00000419235.1	Q9Y4C2-1
	TCAF1	ENST00000355951.2	TSL:1	c.95T>A	p.Ile32Asn	missense	Exon 2 of 9	ENSP00000348220.2	Q9Y4C2-2
	TCAF1	ENST00000872784.1		c.95T>A	p.Ile32Asn	missense	Exon 2 of 9	ENSP00000542843.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000472 AC: 1 AN: 211880 AF XY: 0.00

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: 0.0000101

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1424546 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 706208

African (AFR) AF: 0.00 AC: 0 AN: 32070

American (AMR) AF: 0.00 AC: 0 AN: 38474

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23014

East Asian (EAS) AF: 0.00 AC: 0 AN: 39640

South Asian (SAS) AF: 0.00 AC: 0 AN: 78196

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5538

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1097188

Other (OTH) AF: 0.00 AC: 0 AN: 58800

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.38
BayesDel_addAF	Benign	-0.097	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.13	T
Eigen	Benign	0.082
Eigen_PC	Benign	-0.057
FATHMM_MKL	Benign	0.59	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.27	T
MetaSVM	Benign	-1.1	T
PhyloP100		1.3
PrimateAI	Benign	0.47	T
PROVEAN	Uncertain	-2.6	D
REVEL	Benign	0.14
Sift	Uncertain	0.029	D
Sift4G	Uncertain	0.018	D
Polyphen		0.94	P
Vest4		0.76
MutPred		0.54		Loss of stability (P = 0.0251)
MVP		0.14
MPC		0.14
ClinPred		0.96	D
GERP RS		2.8
Varity_R		0.41
gMVP		0.79
Mutation Taster		=90/10	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: rs746854510; hg19: chr7-143573607;