chr6-31707634-C-T

Position:

chr6-31707634-C-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001003693.3(LY6G6F):c.229C>T(p.Pro77Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000366 in 1,613,646 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000039 ( 2 hom. )

Consequence

LY6G6F
NM_001003693.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.18

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.037226796).

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LY6G6F	NM_001003693.3 link	c.229C>T	p.Pro77Ser	missense_variant	2/6	ENST00000375832.5	NP_001003693.1
LY6G6F-LY6G6D	NM_001353334.2 link	c.229C>T	p.Pro77Ser	missense_variant	2/6		NP_001340263.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
LY6G6F	ENST00000375832.5 link	c.229C>T	p.Pro77Ser	missense_variant	2/6	1	NM_001003693.3	ENSP00000364992.5	Q5SQ64-1
LY6G6F-LY6G6D	ENST00000503322.1 link	c.229C>T	p.Pro77Ser	missense_variant	2/6	1		ENSP00000421232.1
ENSG00000204422	ENST00000461287.1 link	n.537+4383G>A		intron_variant		2

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152216

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000200

AC:

AN:

249568

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

134948

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000581

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000164

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000390

AC:

AN:

1461430

Hom.:

Cov.:

AF XY:

0.0000316

AC XY:

AN XY:

726964

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000672

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.000795

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152216

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74364

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000192

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000214

Hom.:

Bravo

AF:

0.0000491

ExAC

AF:

0.00000824

AC:

Asia WGS

AF:

0.00231

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 02, 2024

The c.229C>T (p.P77S) alteration is located in exon 2 (coding exon 2) of the LY6G6F gene. This alteration results from a C to T substitution at nucleotide position 229, causing the proline (P) at amino acid position 77 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

Benign

0.096

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.62

CADD

Benign

7.1

DANN

Benign

0.93

DEOGEN2

Benign

0.0084

T;.

Eigen

Benign

-0.97

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.016

LIST_S2

Benign

0.63

T;.

M_CAP

Benign

0.0089

MetaRNN

Benign

0.037

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

2.0

M;.

PrimateAI

Benign

0.33

PROVEAN

Uncertain

-2.8

D;N

REVEL

Benign

0.078

Sift

Benign

0.077

T;T

Sift4G

Benign

0.35

T;T

Polyphen

0.0020

B;.

Vest4

0.049

MutPred

0.26

Gain of phosphorylation at P77 (P = 0.0119);Gain of phosphorylation at P77 (P = 0.0119);

MVP

0.21

MPC

0.074

ClinPred

0.095

GERP RS

-6.3

Varity_R

0.047

gMVP

0.23

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over