6-31707604-G-C

Variant names:

• chr6-31707604-G-C
• rs780044897
• NM_001003693.3:c.199G>C

Variant summary

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

The NM_001003693.3(LY6G6F):​c.199G>C​(p.Val67Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,586 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: LY6G6F NM_001003693.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.333

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=0.09040764).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LY6G6F	NM_001003693.3	c.199G>C	p.Val67Leu	missense_variant	Exon 2 of 6	ENST00000375832.5	NP_001003693.1
LY6G6F-LY6G6D	NM_001353334.2	c.199G>C	p.Val67Leu	missense_variant	Exon 2 of 6		NP_001340263.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LY6G6F	ENST00000375832.5	c.199G>C	p.Val67Leu	missense_variant	Exon 2 of 6	1	NM_001003693.3	ENSP00000364992.5
LY6G6F-LY6G6D	ENST00000503322.1	c.199G>C	p.Val67Leu	missense_variant	Exon 2 of 6	1		ENSP00000421232.1
ENSG00000204422	ENST00000461287.1	n.537+4413C>G		intron_variant	Intron 3 of 21	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461586 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727066

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000756

EpiCase AF: 0.00

EpiControl AF: 0.0000594

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 25, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.199G>C (p.V67L) alteration is located in exon 2 (coding exon 2) of the LY6G6F gene. This alteration results from a G to C substitution at nucleotide position 199, causing the valine (V) at amino acid position 67 to be replaced by a leucine (L). 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	0.18
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	11
DANN	Benign	0.97
DEOGEN2	Benign	0.0084	T;.
Eigen	Benign	-0.72
Eigen_PC	Benign	-0.71
FATHMM_MKL	Benign	0.075	N
LIST_S2	Benign	0.67	T;.
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.090	T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Uncertain	2.2	M;.
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-1.9	N;N
REVEL	Benign	0.078
Sift	Benign	0.050	D;D
Sift4G	Benign	0.092	T;T
Polyphen		0.0020	B;.
Vest4		0.080
MutPred		0.57		Loss of sheet (P = 0.0181);Loss of sheet (P = 0.0181);
MVP		0.48
MPC		0.072
ClinPred		0.16	T
GERP RS		2.6
Varity_R		0.035
gMVP		0.27

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs780044897; hg19: chr6-31675381;