6-31707506-C-A

Position:

• chr6-31707506-C-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001003693.3(LY6G6F):​c.101C>A​(p.Pro34Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00353 in 1,614,166 control chromosomes in the GnomAD database, including 101 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.0091 (18 hom., cov: 32)
  • Exomes 𝑓: 0.0030 (83 hom.)
• Consequence: LY6G6F NM_001003693.3 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.60

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 Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.010085255).
• BP6: Variant 6-31707506-C-A is Benign according to our data. Variant chr6-31707506-C-A is described in ClinVar as [Benign]. Clinvar id is 780983.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00905 (1379/152306) while in subpopulation AFR AF= 0.0272 (1129/41548). AF 95% confidence interval is 0.0259. There are 18 homozygotes in gnomad4. There are 664 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 18 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LY6G6F	NM_001003693.3	c.101C>A	p.Pro34Gln	missense_variant	2/6	ENST00000375832.5	NP_001003693.1
LY6G6F-LY6G6D	NM_001353334.2	c.101C>A	p.Pro34Gln	missense_variant	2/6		NP_001340263.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LY6G6F	ENST00000375832.5	c.101C>A	p.Pro34Gln	missense_variant	2/6	1	NM_001003693.3	ENSP00000364992.5
LY6G6F-LY6G6D	ENST00000503322.1	c.101C>A	p.Pro34Gln	missense_variant	2/6	1		ENSP00000421232.1
ENSG00000204422	ENST00000461287.1	n.537+4511G>T		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.00904 AC: 1376 AN: 152188 Hom.: 18 Cov.: 32

Gnomad AFR AF: 0.0272

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00419

Gnomad ASJ AF: 0.00346

Gnomad EAS AF: 0.0129

Gnomad SAS AF: 0.00166

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00109

Gnomad OTH AF: 0.0105

GnomAD3 exomes AF: 0.00439 AC: 1103 AN: 251222 Hom.: 12 AF XY: 0.00360 AC XY: 489 AN XY: 135812

Gnomad AFR exome AF: 0.0318

Gnomad AMR exome AF: 0.00448

Gnomad ASJ exome AF: 0.00179

Gnomad EAS exome AF: 0.0110

Gnomad SAS exome AF: 0.00160

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.00125

Gnomad OTH exome AF: 0.00310

GnomAD4 exome AF: 0.00296 AC: 4320 AN: 1461860 Hom.: 83 Cov.: 32 AF XY: 0.00282 AC XY: 2053 AN XY: 727224

Gnomad4 AFR exome AF: 0.0314

Gnomad4 AMR exome AF: 0.00420

Gnomad4 ASJ exome AF: 0.00222

Gnomad4 EAS exome AF: 0.0434

Gnomad4 SAS exome AF: 0.00183

Gnomad4 FIN exome AF: 0.0000749

Gnomad4 NFE exome AF: 0.000807

Gnomad4 OTH exome AF: 0.00311

GnomAD4 genome AF: 0.00905 AC: 1379 AN: 152306 Hom.: 18 Cov.: 32 AF XY: 0.00892 AC XY: 664 AN XY: 74476

Gnomad4 AFR AF: 0.0272

Gnomad4 AMR AF: 0.00418

Gnomad4 ASJ AF: 0.00346

Gnomad4 EAS AF: 0.0129

Gnomad4 SAS AF: 0.00145

Gnomad4 FIN AF: 0.0000941

Gnomad4 NFE AF: 0.00109

Gnomad4 OTH AF: 0.0104

Alfa AF: 0.00369 Hom.: 52

Bravo AF: 0.0101

TwinsUK AF: 0.000809 AC: 3

ALSPAC AF: 0.000778 AC: 3

ESP6500AA AF: 0.0325 AC: 143

ESP6500EA AF: 0.000581 AC: 5

ExAC AF: 0.00501 AC: 608

Asia WGS AF: 0.0110 AC: 39 AN: 3478

EpiCase AF: 0.00174

EpiControl AF: 0.00207

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 20, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.34
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.31
CADD	Uncertain	25
DANN	Benign	0.97
DEOGEN2	Benign	0.042	T;.
Eigen	Uncertain	0.56
Eigen_PC	Uncertain	0.52
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.61	T;.
MetaRNN	Benign	0.010	T;T
MetaSVM	Benign	-0.60	T
MutationAssessor	Uncertain	2.2	M;.
PrimateAI	Benign	0.42	T
PROVEAN	Pathogenic	-5.2	D;D
REVEL	Benign	0.14
Sift	Uncertain	0.0030	D;D
Sift4G	Uncertain	0.0090	D;D
Polyphen		0.99	D;.
Vest4		0.53
MVP		0.80
MPC		0.41
ClinPred		0.033	T
GERP RS		4.8
Varity_R		0.14
gMVP		0.39

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

Other links and lift over

dbSNP: rs17200983; hg19: chr6-31675283;