rs4682357

Variant names:

• chr3-112095870-G-A
• rs4682357
• NM_024616.3:c.268+2381G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_024616.3(C3orf52):​c.268+2381G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.529 in 151,746 control chromosomes in the GnomAD database, including 22,956 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.53 (22956 hom., cov: 30)
• Consequence: C3orf52 NM_024616.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.302
• Publications: 5 publications found

Genes affected

C3orf52 (HGNC:26255): (chromosome 3 open reading frame 52) Predicted to be located in endoplasmic reticulum membrane. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

C3orf52 Gene-Disease associations (from GenCC):

• hypotrichosis 15

  Inheritance: AR Classification: STRONG, MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.736 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C3orf52	NM_024616.3	c.268+2381G>A		intron_variant	Intron 2 of 5	ENST00000264848.10	NP_078892.3
C3orf52	NM_001171747.2	c.268+2381G>A		intron_variant	Intron 2 of 3		NP_001165218.1
C3orf52	XR_007095726.1	n.287+2381G>A		intron_variant	Intron 2 of 7
C3orf52	XR_924171.4	n.287+2381G>A		intron_variant	Intron 2 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C3orf52	ENST00000264848.10	c.268+2381G>A		intron_variant	Intron 2 of 5	1	NM_024616.3	ENSP00000264848.5

Frequencies

GnomAD3 genomes AF: 0.529 AC: 80235 AN: 151630 Hom.: 22948 Cov.: 30

Gnomad AFR AF: 0.283

Gnomad AMI AF: 0.618

Gnomad AMR AF: 0.620

Gnomad ASJ AF: 0.514

Gnomad EAS AF: 0.755

Gnomad SAS AF: 0.599

Gnomad FIN AF: 0.618

Gnomad MID AF: 0.522

Gnomad NFE AF: 0.621

Gnomad OTH AF: 0.548

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.529 AC: 80265 AN: 151746 Hom.: 22956 Cov.: 30 AF XY: 0.535 AC XY: 39643 AN XY: 74164

African (AFR) AF: 0.283 AC: 11701 AN: 41326

American (AMR) AF: 0.621 AC: 9461 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.514 AC: 1783 AN: 3468

East Asian (EAS) AF: 0.756 AC: 3885 AN: 5138

South Asian (SAS) AF: 0.598 AC: 2872 AN: 4800

European-Finnish (FIN) AF: 0.618 AC: 6503 AN: 10524

Middle Eastern (MID) AF: 0.507 AC: 149 AN: 294

European-Non Finnish (NFE) AF: 0.621 AC: 42187 AN: 67940

Other (OTH) AF: 0.552 AC: 1160 AN: 2100

Alfa AF: 0.591 Hom.: 13627

Bravo AF: 0.519

Asia WGS AF: 0.644 AC: 2242 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.4
DANN	Benign	0.58
PhyloP100		0.30
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs4682357; hg19: chr3-111814717;