6-31715390-C-G

Variant names:

• chr6-31715390-C-G
• rs1806344467
• NM_021246.4:c.35C>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_021246.4(LY6G6D):​c.35C>G​(p.Ser12Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: LY6G6D NM_021246.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.15

Genes affected

LY6G6D (HGNC:13935): (lymphocyte antigen 6 family member G6D) LY6G6D 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, Apr 2009]

LY6G6F-LY6G6D (HGNC:38821): (LY6G6F-LY6G6D readthrough) This locus represents naturally occurring readthrough transcription between the neighboring LY6G6F (lymphocyte antigen 6 family member G6F) and LY6G6D (lymphocyte antigen 6 family member G6D) genes on chromosome 6. The readthrough transcript encodes a fusion protein that shares sequence identity with each individual gene product. [provided by RefSeq, Jul 2017]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21371037).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LY6G6D	NM_021246.4	c.35C>G	p.Ser12Cys	missense_variant	Exon 1 of 3	ENST00000375825.8	NP_067069.2
LY6G6F-LY6G6D	NM_001353334.2	c.803-112C>G		intron_variant	Intron 4 of 5		NP_001340263.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LY6G6D	ENST00000375825.8	c.35C>G	p.Ser12Cys	missense_variant	Exon 1 of 3	1	NM_021246.4	ENSP00000364985.3
LY6G6D	ENST00000375824.1	c.35C>G	p.Ser12Cys	missense_variant	Exon 1 of 3	1		ENSP00000364984.1
LY6G6F-LY6G6D	ENST00000503322.1	c.803-112C>G		intron_variant	Intron 4 of 5	1		ENSP00000421232.1
LY6G6D	ENST00000479334.1	n.35C>G		non_coding_transcript_exon_variant	Exon 1 of 2	1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 09, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.35C>G (p.S12C) alteration is located in exon 1 (coding exon 1) of the LY6G6D gene. This alteration results from a C to G substitution at nucleotide position 35, causing the serine (S) at amino acid position 12 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.094
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	19
DANN	Uncertain	0.98
DEOGEN2	Benign	0.060	T;.
Eigen	Benign	0.072
Eigen_PC	Benign	0.11
FATHMM_MKL	Benign	0.32	N
M_CAP	Benign	0.0066	T
MetaRNN	Benign	0.21	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.34	N;.
PROVEAN	Benign	-1.9	N;N
REVEL	Benign	0.089
Sift	Benign	0.066	T;D
Sift4G	Uncertain	0.028	D;D
Polyphen		0.88	P;.
Vest4		0.22
MutPred		0.33		Loss of stability (P = 0.0877);Loss of stability (P = 0.0877);
MVP		0.36
MPC		0.39
ClinPred		0.37	T
GERP RS		4.3
Varity_R		0.11
gMVP		0.38

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: rs1806344467; hg19: chr6-31683167;