rs142539094

Variant names:

• chr7-143724382-C-T
• rs142539094
• NM_001363538.2:c.2190C>T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_001363538.2(TCAF2):​c.2190C>T​(p.Pro730Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00409 in 1,596,948 control chromosomes in the GnomAD database, including 185 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.018 (75 hom., cov: 20)
  • Exomes 𝑓: 0.0028 (110 hom.)
• Consequence: TCAF2 NM_001363538.2 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0220
• Publications: 2 publications found

Genes affected

TCAF2 (HGNC:26878): (TRPM8 channel associated factor 2) Enables transmembrane transporter binding activity. Involved in negative regulation of anion channel activity; positive regulation of cell migration; and positive regulation of protein targeting to membrane. Located in cell junction and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000291149 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.179).
• BP6: Variant 7-143724382-C-T is Benign according to our data. Variant chr7-143724382-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 403526.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.022 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.055 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001363538.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TCAF2	NM_001363538.2	MANE Select	c.2190C>T	p.Pro730Pro	synonymous	Exon 7 of 8	NP_001350467.1
	TCAF2	NM_001438662.2		c.2190C>T	p.Pro730Pro	synonymous	Exon 7 of 8	NP_001425591.2
	TCAF2	NM_001438663.2		c.2190C>T	p.Pro730Pro	synonymous	Exon 8 of 9	NP_001425592.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TCAF2	ENST00000684770.1	MANE Select	c.2190C>T	p.Pro730Pro	synonymous	Exon 7 of 8	ENSP00000506869.1
	TCAF2	ENST00000357344.9	TSL:1	c.2190C>T	p.Pro730Pro	synonymous	Exon 6 of 6	ENSP00000349902.4
	TCAF2	ENST00000441159.7	TSL:5	c.2190C>T	p.Pro730Pro	synonymous	Exon 6 of 7	ENSP00000404265.2

Frequencies

GnomAD3 genomes AF: 0.0175 AC: 2515 AN: 143446 Hom.: 75 Cov.: 20

Gnomad AFR AF: 0.0570

Gnomad AMI AF: 0.00111

Gnomad AMR AF: 0.0108

Gnomad ASJ AF: 0.0154

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000935

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0267

Gnomad NFE AF: 0.000798

Gnomad OTH AF: 0.0181

GnomAD2 exomes AF: 0.00839 AC: 478 AN: 56954 AF XY: 0.00758

Gnomad AFR exome AF: 0.0626

Gnomad AMR exome AF: 0.00845

Gnomad ASJ exome AF: 0.0128

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00133

Gnomad OTH exome AF: 0.00573

GnomAD4 exome AF: 0.00276 AC: 4016 AN: 1453394 Hom.: 110 Cov.: 30 AF XY: 0.00256 AC XY: 1847 AN XY: 722874

African (AFR) AF: 0.0628 AC: 2091 AN: 33302

American (AMR) AF: 0.00702 AC: 312 AN: 44474

Ashkenazi Jewish (ASJ) AF: 0.0142 AC: 371 AN: 26042

East Asian (EAS) AF: 0.00 AC: 0 AN: 39674

South Asian (SAS) AF: 0.000502 AC: 43 AN: 85598

European-Finnish (FIN) AF: 0.0000943 AC: 5 AN: 52998

Middle Eastern (MID) AF: 0.0167 AC: 69 AN: 4134

European-Non Finnish (NFE) AF: 0.000619 AC: 685 AN: 1107218

Other (OTH) AF: 0.00734 AC: 440 AN: 59954

GnomAD4 genome AF: 0.0176 AC: 2521 AN: 143554 Hom.: 75 Cov.: 20 AF XY: 0.0171 AC XY: 1191 AN XY: 69608

African (AFR) AF: 0.0570 AC: 2214 AN: 38842

American (AMR) AF: 0.0108 AC: 156 AN: 14410

Ashkenazi Jewish (ASJ) AF: 0.0154 AC: 52 AN: 3372

East Asian (EAS) AF: 0.00 AC: 0 AN: 4900

South Asian (SAS) AF: 0.000936 AC: 4 AN: 4272

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9452

Middle Eastern (MID) AF: 0.0250 AC: 7 AN: 280

European-Non Finnish (NFE) AF: 0.000798 AC: 52 AN: 65166

Other (OTH) AF: 0.0178 AC: 35 AN: 1962

Alfa AF: 0.0123 Hom.: 2

Bravo AF: 0.0215

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Silent variant not near splice site

not provided Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
CADD	Benign	8.3
DANN	Benign	0.81
PhyloP100		0.022
Mutation Taster		=98/2	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs142539094; hg19: chr7-143421475;