Genetic Variant NM_001003693.3:c.272T>C (chr6-31707677-T-C) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_001003693.3(LY6G6F):c.272T>C(p.Leu91Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.78

Variant links:

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 links:

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]

LY6G6F-LY6G6D links:

ENSG00000204422 (HGNC:):

ENSG00000204422 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.816

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LY6G6F	NM_001003693.3 link	c.272T>C	p.Leu91Ser	missense_variant	Exon 2 of 6	ENST00000375832.5	NP_001003693.1
LY6G6F-LY6G6D	NM_001353334.2 link	c.272T>C	p.Leu91Ser	missense_variant	Exon 2 of 6		NP_001340263.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
LY6G6F	ENST00000375832.5 link	c.272T>C	p.Leu91Ser	missense_variant	Exon 2 of 6	1	NM_001003693.3	ENSP00000364992.5	Q5SQ64-1
LY6G6F-LY6G6D	ENST00000503322.1 link	c.272T>C	p.Leu91Ser	missense_variant	Exon 2 of 6	1		ENSP00000421232.1
ENSG00000204422	ENST00000461287.1 link	n.537+4340A>G		intron_variant	Intron 3 of 21	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 30, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.272T>C (p.L91S) alteration is located in exon 2 (coding exon 2) of the LY6G6F gene. This alteration results from a T to C substitution at nucleotide position 272, causing the leucine (L) at amino acid position 91 to be replaced by a serine (S). 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

Pathogenic

0.98

BayesDel_addAF

Pathogenic

0.22

BayesDel_noAF

Uncertain

0.080

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.22

T;.

Eigen

Uncertain

0.58

Eigen_PC

Uncertain

0.53

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.76

T;.

M_CAP

Benign

0.021

MetaRNN

Pathogenic

0.82

D;D

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.2

M;.

PrimateAI

Uncertain

0.50

PROVEAN

Pathogenic

-5.5

D;D

REVEL

Benign

0.28

Sift

Pathogenic

0.0

D;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

1.0

D;.

Vest4

0.90

MutPred

0.57

Loss of sheet (P = 0.0054);Loss of sheet (P = 0.0054);

MVP

0.37

MPC

0.48

ClinPred

1.0

GERP RS

5.4

Varity_R

0.22

gMVP

0.84

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over