6-6649629-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_004271.4(LY86):c.357G>T(p.Gln119His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000355 in 1,408,110 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q119R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0000036 (0 hom.)
• Consequence: LY86 NM_004271.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.931

Genes affected

LY86 (HGNC:16837): (lymphocyte antigen 86) Acts upstream of or within positive regulation of lipopolysaccharide-mediated signaling pathway. Predicted to be located in extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.40529874).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LY86	NM_004271.4	c.357G>T	p.Gln119His	missense_variant	4/5	ENST00000230568.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LY86	ENST00000230568.5	c.357G>T	p.Gln119His	missense_variant	4/5	1	NM_004271.4	P1
LY86	ENST00000379953.6	c.357G>T	p.Gln119His	missense_variant	5/6	5		P1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 0.00000355 AC: 5 AN: 1408110 Hom.: 0 Cov.: 25 AF XY: 0.00000142 AC XY: 1 AN XY: 703214

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: 0.00000466

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 34

Alfa AF: 0.0000363 Hom.: 0

Bravo AF: 0.0000151

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 08, 2024

The c.357G>T (p.Q119H) alteration is located in exon 4 (coding exon 4) of the LY86 gene. This alteration results from a G to T substitution at nucleotide position 357, causing the glutamine (Q) at amino acid position 119 to be replaced by a histidine (H). 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	Uncertain	0.51
BayesDel_addAF	Benign	-0.098	T
BayesDel_noAF	Benign	-0.38
Cadd	Benign	19
Dann	Uncertain	1.0
DEOGEN2	Benign	0.23	T;T
Eigen	Benign	0.18
Eigen_PC	Benign	0.14
FATHMM_MKL	Benign	0.75	D
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.41	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.9	L;L
MutationTaster	Benign	0.94	N;N
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-1.2	N;N
REVEL	Benign	0.18
Sift	Benign	0.50	T;T
Sift4G	Uncertain	0.012	D;D
Polyphen		1.0	D;D
Vest4		0.33
MutPred		0.40		Gain of methylation at R114 (P = 0.0536);Gain of methylation at R114 (P = 0.0536);
MVP		0.59
MPC		0.057
ClinPred		0.79	D
GERP RS		2.4
Varity_R		0.13
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: rs779087389; hg19: chr6-6649862;