6-31707930-G-A

Variant names:

• chr6-31707930-G-A
• NM_001003693.3:c.442G>A

Variant summary

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

The NM_001003693.3(LY6G6F):​c.442G>A​(p.Val148Met) 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. 12/21 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: not found (cov: 32)
• Consequence: LY6G6F NM_001003693.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.98

Genes affected

LY6G6F (HGNC:13933): (lymphocyte antigen 6 family member G6F) The human G6f protein is a type I transmembrane protein belonging to the immunoglobin (Ig) superfamily, which is comprised of cell-surface proteins involved in the immune system and cellular recognition (de Vet et al., 2003 [PubMed 12852788]).[supplied by OMIM, Mar 2008]

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]

ENSG00000204422 (HGNC:):

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=0.23367852).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LY6G6F	NM_001003693.3	c.442G>A	p.Val148Met	missense_variant	Exon 3 of 6	ENST00000375832.5	NP_001003693.1
LY6G6F-LY6G6D	NM_001353334.2	c.442G>A	p.Val148Met	missense_variant	Exon 3 of 6		NP_001340263.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LY6G6F	ENST00000375832.5	c.442G>A	p.Val148Met	missense_variant	Exon 3 of 6	1	NM_001003693.3	ENSP00000364992.5
LY6G6F-LY6G6D	ENST00000503322.1	c.442G>A	p.Val148Met	missense_variant	Exon 3 of 6	1		ENSP00000421232.1
ENSG00000204422	ENST00000461287.1	n.537+4087C>T		intron_variant	Intron 3 of 21	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 12, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.442G>A (p.V148M) alteration is located in exon 3 (coding exon 3) of the LY6G6F gene. This alteration results from a G to A substitution at nucleotide position 442, causing the valine (V) at amino acid position 148 to be replaced by a methionine (M). 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	0.14
BayesDel_addAF	Benign	-0.075	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.010	T;.
Eigen	Uncertain	0.32
Eigen_PC	Uncertain	0.32
FATHMM_MKL	Benign	0.69	D
LIST_S2	Uncertain	0.89	D;.
M_CAP	Benign	0.0060	T
MetaRNN	Benign	0.23	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.4	M;.
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-2.1	N;N
REVEL	Benign	0.096
Sift	Uncertain	0.0040	D;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		0.92	P;.
Vest4		0.24
MutPred		0.59		Gain of disorder (P = 0.0937);Gain of disorder (P = 0.0937);
MVP		0.28
MPC		0.36
ClinPred		0.95	D
GERP RS		4.6
Varity_R		0.14
gMVP		0.45

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-31675707;