rs13077498

Variant names:

• chr3-49276545-C-T
• rs13077498
• NM_198562.3:c.328G>A

Variant summary

Our verdict is Benign. The variant received -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. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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
• Publications: 37 publications found

Genes affected

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

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198562.3. 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
	C3orf62	NM_198562.3	MANE Select	c.328G>A	p.Glu110Lys	missense	Exon 1 of 3	NP_940964.1	Q6ZUJ4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C3orf62	ENST00000343010.8	TSL:1 MANE Select	c.328G>A	p.Glu110Lys	missense	Exon 1 of 3	ENSP00000341139.3	Q6ZUJ4
	C3orf62	ENST00000436325.1	TSL:4	c.322G>A	p.Glu108Lys	missense	Exon 2 of 4	ENSP00000413663.1	C9JW57
	C3orf62	ENST00000424960.1	TSL:5	n.267+31G>A		intron	N/A	ENSP00000391945.1	H7BZX3

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

GnomAD2 exomes AF: 0.0880 AC: 22127 AN: 251494 AF XY: 0.0873

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 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

African (AFR) AF: 0.0817 AC: 2734 AN: 33480

American (AMR) AF: 0.0544 AC: 2435 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.123 AC: 3208 AN: 26136

East Asian (EAS) AF: 0.0403 AC: 1599 AN: 39700

South Asian (SAS) AF: 0.0582 AC: 5018 AN: 86256

European-Finnish (FIN) AF: 0.119 AC: 6375 AN: 53418

Middle Eastern (MID) AF: 0.0810 AC: 467 AN: 5768

European-Non Finnish (NFE) AF: 0.108 AC: 120178 AN: 1111994

Other (OTH) AF: 0.0955 AC: 5765 AN: 60392

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

African (AFR) AF: 0.0835 AC: 3466 AN: 41520

American (AMR) AF: 0.0758 AC: 1159 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.126 AC: 439 AN: 3472

East Asian (EAS) AF: 0.0347 AC: 180 AN: 5180

South Asian (SAS) AF: 0.0601 AC: 290 AN: 4828

European-Finnish (FIN) AF: 0.114 AC: 1210 AN: 10588

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.105 AC: 7144 AN: 68028

Other (OTH) AF: 0.0956 AC: 202 AN: 2114

Alfa AF: 0.101 Hom.: 2452

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 v4.9

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
Eigen	Benign	-1.9
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.0088	N
LIST_S2	Benign	0.60	T
MetaRNN	Benign	0.0011	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.90	N
PhyloP100		-1.3
PROVEAN	Benign	1.4	N
REVEL	Benign	0.094
Sift	Benign	1.0	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
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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