rs928946

chr3-50286511-G-Achr3-50286511-G-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_153215.3(LSMEM2):c.99G>A(p.Gly33=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00648 in 1,610,978 control chromosomes in the GnomAD database, including 622 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.034 (312 hom., cov: 33)
  • Exomes 𝑓: 0.0036 (310 hom.)
• Consequence: LSMEM2 NM_153215.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.00

Genes affected

LSMEM2 (HGNC:26781): (leucine rich single-pass membrane protein 2) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP7: Synonymous conserved (PhyloP=-1 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.117 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LSMEM2	NM_153215.3	c.99G>A	p.Gly33=	synonymous_variant	2/4	ENST00000316436.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LSMEM2	ENST00000316436.4	c.99G>A	p.Gly33=	synonymous_variant	2/4	1	NM_153215.3	P1

Frequencies

GnomAD3 genomes AF: 0.0344 AC: 5236 AN: 152216 Hom.: 312 Cov.: 33

Gnomad AFR AF: 0.119

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0134

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00166

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000353

Gnomad OTH AF: 0.0229

GnomAD3 exomes AF: 0.00778 AC: 1899 AN: 244034 Hom.: 108 AF XY: 0.00558 AC XY: 739 AN XY: 132466

Gnomad AFR exome AF: 0.112

Gnomad AMR exome AF: 0.00403

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000234

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000127

Gnomad OTH exome AF: 0.00468

GnomAD4 exome AF: 0.00355 AC: 5185 AN: 1458644 Hom.: 310 Cov.: 33 AF XY: 0.00292 AC XY: 2119 AN XY: 725388

Gnomad4 AFR exome AF: 0.131

Gnomad4 AMR exome AF: 0.00487

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000502

Gnomad4 FIN exome AF: 0.0000189

Gnomad4 NFE exome AF: 0.0000711

Gnomad4 OTH exome AF: 0.00767

GnomAD4 genome AF: 0.0345 AC: 5254 AN: 152334 Hom.: 312 Cov.: 33 AF XY: 0.0327 AC XY: 2437 AN XY: 74496

Gnomad4 AFR AF: 0.120

Gnomad4 AMR AF: 0.0134

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00166

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000353

Gnomad4 OTH AF: 0.0227

Alfa AF: 0.0104 Hom.: 39

Bravo AF: 0.0387

Asia WGS AF: 0.00635 AC: 23 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	0.18
Dann	Benign	0.77

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs928946; hg19: chr3-50323942;