dbSNP rs142539094: TCAF2:p.Pro730Pro (chr7-143724382-C-T) – ACMG Classification: Benign (-19 pts)

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

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

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.0220

Publications

2 publications found

Variant links:

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]

TCAF2 links:

ENSG00000291149 (HGNC:):

ENSG00000291149 links:

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ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TCAF2	NM_001363538.2 link	c.2190C>T	p.Pro730Pro	synonymous_variant	Exon 7 of 8	ENST00000684770.1	NP_001350467.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TCAF2	ENST00000684770.1 link	c.2190C>T	p.Pro730Pro	synonymous_variant	Exon 7 of 8		NM_001363538.2	ENSP00000506869.1		A6NFQ2-1

Frequencies

GnomAD3 genomes

AF:

0.0175

AC:

2515

AN:

143446

Hom.:

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.00256

AC XY:

1847

AN XY:

722874

show subpopulations

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:

AN:

39674

South Asian (SAS)

AF:

0.000502

AC:

AN:

85598

European-Finnish (FIN)

AF:

0.0000943

AC:

AN:

52998

Middle Eastern (MID)

AF:

0.0167

AC:

AN:

4134

European-Non Finnish (NFE)

AF:

0.000619

AC:

685

AN:

1107218

Other (OTH)

AF:

0.00734

AC:

440

AN:

59954

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

Heterozygous variant carriers

174

349

523

698

872

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

160

240

320

400

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0176

AC:

2521

AN:

143554

Hom.:

Cov.:

AF XY:

0.0171

AC XY:

1191

AN XY:

69608

show subpopulations

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:

AN:

3372

East Asian (EAS)

AF:

0.00

AC:

AN:

4900

South Asian (SAS)

AF:

0.000936

AC:

AN:

4272

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9452

Middle Eastern (MID)

AF:

0.0250

AC:

AN:

280

European-Non Finnish (NFE)

AF:

0.000798

AC:

AN:

65166

Other (OTH)

AF:

0.0178

AC:

AN:

1962

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

102

203

305

406

508

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

112

140

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0123

Hom.:

Bravo

AF:

0.0215

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

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 v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.42

CADD

Benign

8.3

(source)

DANN

Benign

0.81

PhyloP100

0.022

Mutation Taster

=98/2

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over