Genetic Variant C3orf62:p.Val60Met (chr3-49276695-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_198562.3(C3orf62):c.178G>A(p.Val60Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00437 in 1,614,166 control chromosomes in the GnomAD database, including 268 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.023 ( 149 hom., cov: 32)

Exomes 𝑓: 0.0024 ( 119 hom. )

Consequence

C3orf62
NM_198562.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.56

Variant links:

Genes affected

C3orf62 (HGNC:24771): (chromosome 3 open reading frame 62)

C3orf62 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0016271472).

BP6

Variant 3-49276695-C-T is Benign according to our data. Variant chr3-49276695-C-T is described in ClinVar as [Benign]. Clinvar id is 775870.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0789 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C3orf62	NM_198562.3 link	c.178G>A	p.Val60Met	missense_variant	Exon 1 of 3	ENST00000343010.8	NP_940964.1	Q6ZUJ4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
C3orf62	ENST00000343010.8 link	c.178G>A	p.Val60Met	missense_variant	Exon 1 of 3	1	NM_198562.3	ENSP00000341139.3	Q6ZUJ4
C3orf62	ENST00000436325.1 link	c.172G>A	p.Val58Met	missense_variant	Exon 2 of 4	4		ENSP00000413663.1	C9JW57
C3orf62	ENST00000424960.1 link	n.148G>A		non_coding_transcript_exon_variant	Exon 1 of 3	5		ENSP00000391945.1	H7BZX3

Frequencies

GnomAD3 genomes

AF:

0.0233

AC:

3550

AN:

152168

Hom.:

149

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0814

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00772

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00250

Gnomad SAS

AF:

0.00103

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000250

Gnomad OTH

AF:

0.0134

GnomAD3 exomes

AF:

0.00621

AC:

1560

AN:

251374

Hom.:

AF XY:

0.00474

AC XY:

644

AN XY:

135866

show subpopulations

Gnomad AFR exome

AF:

0.0831

Gnomad AMR exome

AF:

0.00396

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00158

Gnomad SAS exome

AF:

0.000163

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000176

Gnomad OTH exome

AF:

0.00310

GnomAD4 exome

AF:

0.00239

AC:

3498

AN:

1461880

Hom.:

119

Cov.:

AF XY:

0.00206

AC XY:

1501

AN XY:

727242

show subpopulations

Gnomad4 AFR exome

AF:

0.0824

Gnomad4 AMR exome

AF:

0.00434

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00103

Gnomad4 SAS exome

AF:

0.000383

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000127

Gnomad4 OTH exome

AF:

0.00530

GnomAD4 genome

AF:

0.0233

AC:

3554

AN:

152286

Hom.:

149

Cov.:

AF XY:

0.0230

AC XY:

1715

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.0812

Gnomad4 AMR

AF:

0.00771

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00251

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000250

Gnomad4 OTH

AF:

0.0132

Alfa

AF:

0.0106

Hom.:

Bravo

AF:

0.0260

ESP6500AA

AF:

0.0776

AC:

342

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.00764

AC:

927

Asia WGS

AF:

0.00722

AC:

AN:

3478

EpiCase

AF:

0.000218

EpiControl

AF:

0.000593

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Aug 03, 2017

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.090

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.42

CADD

Benign

0.27

DANN

Benign

0.89

DEOGEN2

Benign

0.0016

T;T

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.023

LIST_S2

Benign

0.59

T;T

MetaRNN

Benign

0.0016

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

N;.

PROVEAN

Benign

-0.15

N;N

REVEL

Benign

0.020

Sift

Benign

0.22

T;T

Sift4G

Benign

0.23

T;.

Polyphen

0.028

B;.

Vest4

0.037

MVP

0.17

MPC

0.063

ClinPred

0.0060

GERP RS

-1.8

Varity_R

0.038

gMVP

0.10

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over