rs13077498

Positions:

• chr3-49276545-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_198562.3(C3orf62):​c.328G>A​(p.Glu110Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.1 in 1,614,096 control chromosomes in the GnomAD database, including 8,566 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 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 nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.093 (737 hom., cov: 32)
  • Exomes 𝑓: 0.10 (7829 hom.)
• Consequence: C3orf62 NM_198562.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.27

Genes affected

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

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0011317432).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.103 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
C3orf62	NM_198562.3	c.328G>A	p.Glu110Lys	missense_variant	1/3	ENST00000343010.8	NP_940964.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
C3orf62	ENST00000343010.8	c.328G>A	p.Glu110Lys	missense_variant	1/3	1	NM_198562.3	ENSP00000341139.3
C3orf62	ENST00000436325.1	c.322G>A	p.Glu108Lys	missense_variant	2/4	4		ENSP00000413663.1
C3orf62	ENST00000424960.1	n.267+31G>A		intron_variant		5		ENSP00000391945.1

Frequencies

GnomAD3 genomes AF: 0.0934 AC: 14200 AN: 152110 Hom.: 737 Cov.: 32

Gnomad AFR AF: 0.0837

Gnomad AMI AF: 0.0866

Gnomad AMR AF: 0.0759

Gnomad ASJ AF: 0.126

Gnomad EAS AF: 0.0345

Gnomad SAS AF: 0.0600

Gnomad FIN AF: 0.114

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.105

Gnomad OTH AF: 0.0966

GnomAD3 exomes AF: 0.0880 AC: 22127 AN: 251494 Hom.: 1100 AF XY: 0.0873 AC XY: 11863 AN XY: 135922

Gnomad AFR exome AF: 0.0816

Gnomad AMR exome AF: 0.0511

Gnomad ASJ exome AF: 0.125

Gnomad EAS exome AF: 0.0344

Gnomad SAS exome AF: 0.0573

Gnomad FIN exome AF: 0.118

Gnomad NFE exome AF: 0.108

Gnomad OTH exome AF: 0.0963

GnomAD4 exome AF: 0.101 AC: 147779 AN: 1461868 Hom.: 7829 Cov.: 32 AF XY: 0.0996 AC XY: 72423 AN XY: 727234

Gnomad4 AFR exome AF: 0.0817

Gnomad4 AMR exome AF: 0.0544

Gnomad4 ASJ exome AF: 0.123

Gnomad4 EAS exome AF: 0.0403

Gnomad4 SAS exome AF: 0.0582

Gnomad4 FIN exome AF: 0.119

Gnomad4 NFE exome AF: 0.108

Gnomad4 OTH exome AF: 0.0955

GnomAD4 genome AF: 0.0933 AC: 14201 AN: 152228 Hom.: 737 Cov.: 32 AF XY: 0.0927 AC XY: 6897 AN XY: 74416

Gnomad4 AFR AF: 0.0835

Gnomad4 AMR AF: 0.0758

Gnomad4 ASJ AF: 0.126

Gnomad4 EAS AF: 0.0347

Gnomad4 SAS AF: 0.0601

Gnomad4 FIN AF: 0.114

Gnomad4 NFE AF: 0.105

Gnomad4 OTH AF: 0.0956

Alfa AF: 0.104 Hom.: 1862

Bravo AF: 0.0897

TwinsUK AF: 0.115 AC: 427

ALSPAC AF: 0.105 AC: 406

ESP6500AA AF: 0.0872 AC: 384

ESP6500EA AF: 0.108 AC: 932

ExAC AF: 0.0882 AC: 10709

Asia WGS AF: 0.0530 AC: 187 AN: 3478

EpiCase AF: 0.109

EpiControl AF: 0.110

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.067
BayesDel_addAF	Benign	-0.58	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	0.18
DANN	Benign	0.87
DEOGEN2	Benign	0.0013	T;T
Eigen	Benign	-1.9
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.0088	N
LIST_S2	Benign	0.60	T;T
MetaRNN	Benign	0.0011	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.90	N;.
PROVEAN	Benign	1.4	N;N
REVEL	Benign	0.094
Sift	Benign	1.0	T;T
Sift4G	Benign	1.0	T;.
Polyphen		0.0	B;.
Vest4		0.014
MPC		0.066
ClinPred		0.0067	T
GERP RS		-7.3
Varity_R		0.11
gMVP		0.065

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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

Other links and lift over

dbSNP: rs13077498; hg19: chr3-49313978; COSMIC: COSV55535596; COSMIC: COSV55535596;