3-112109580-GTTATT-G

Position:

• chr3-112109580-GTTATT-G

Variant summary

Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1 PM2 PP5

The NM_024616.3(C3orf52):​c.438_442delTTTTA​(p.Thr148fs) variant causes a frameshift change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: C3orf52 NM_024616.3 frameshift
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 4.01

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 (HGNC:):

ACMG classification

Verdict is Pathogenic. Variant got 11 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 3-112109580-GTTATT-G is Pathogenic according to our data. Variant chr3-112109580-GTTATT-G is described in ClinVar as [Pathogenic]. Clinvar id is 1806470.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
C3orf52	NM_024616.3	c.438_442delTTTTA	p.Thr148fs	frameshift_variant	4/6	ENST00000264848.10	NP_078892.3
C3orf52	NM_001171747.2	c.396+6619_396+6623delTTTTA		intron_variant			NP_001165218.1
C3orf52	XR_007095726.1	n.457_461delTTTTA		non_coding_transcript_exon_variant	4/8
C3orf52	XR_924171.4	n.457_461delTTTTA		non_coding_transcript_exon_variant	4/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
C3orf52	ENST00000264848.10	c.438_442delTTTTA	p.Thr148fs	frameshift_variant	4/6	1	NM_024616.3	ENSP00000264848.5

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Hypotrichosis 15 Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Dec 21, 2022

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-111828427;