chr6-31718720-G-C

Variant names:

• chr6-31718720-G-C
• rs15574
• NM_025261.3:c.*376C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_025261.3(LY6G6C):​c.*376C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000143 in 139,854 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 30)
  • Exomes 𝑓: 0.000014 (0 hom.)
• Consequence: LY6G6C NM_025261.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.147
• Publications: 29 publications found

Genes affected

LY6G6C (HGNC:13936): (lymphocyte antigen 6 family member G6C) LY6G6C belongs to a cluster of leukocyte antigen-6 (LY6) genes located in the major histocompatibility complex (MHC) class III region on chromosome 6. Members of the LY6 superfamily typically contain 70 to 80 amino acids, including 8 to 10 cysteines. Most LY6 proteins are attached to the cell surface by a glycosylphosphatidylinositol (GPI) anchor that is directly involved in signal transduction (Mallya et al., 2002 [PubMed 12079290]).[supplied by OMIM, Mar 2008]

MPIG6B (HGNC:13937): (megakaryocyte and platelet inhibitory receptor G6b) This gene is a member of the immunoglobulin (Ig) superfamily and is located in the major histocompatibility complex (MHC) class III region. The protein encoded by this gene is a glycosylated, plasma membrane-bound cell surface receptor, but soluble isoforms encoded by some transcript variants have been found in the endoplasmic reticulum and Golgi before being secreted. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

MPIG6B Gene-Disease associations (from GenCC):

• thrombocytopenia, anemia, and myelofibrosis

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LY6G6C	NM_025261.3	c.*376C>G		3_prime_UTR_variant	Exon 3 of 3	ENST00000375819.3	NP_079537.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LY6G6C	ENST00000375819.3	c.*376C>G		3_prime_UTR_variant	Exon 3 of 3	1	NM_025261.3	ENSP00000364978.2
LY6G6C	ENST00000495859.1	c.*376C>G		3_prime_UTR_variant	Exon 4 of 4	1		ENSP00000433207.1
MPIG6B	ENST00000460663.5	n.90+37G>C		intron_variant	Intron 1 of 6	3

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 0.0000143 AC: 2 AN: 139854 Hom.: 0 Cov.: 0 AF XY: 0.0000143 AC XY: 1 AN XY: 70118

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 5028

American (AMR) AF: 0.00 AC: 0 AN: 6224

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 5688

East Asian (EAS) AF: 0.00 AC: 0 AN: 12816

South Asian (SAS) AF: 0.00 AC: 0 AN: 3018

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 7898

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 734

European-Non Finnish (NFE) AF: 0.0000225 AC: 2 AN: 88800

Other (OTH) AF: 0.00 AC: 0 AN: 9648

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.038550), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 30

Alfa AF: 0.00 Hom.: 16605

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.1
DANN	Benign	0.74
PhyloP100		-0.15

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: rs15574; hg19: chr6-31686497;