3-50286733-G-A

Variant names:

• chr3-50286733-G-A
• rs151106412
• NM_153215.3:c.232G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_153215.3(LSMEM2):​c.232G>A​(p.Val78Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000199 in 1,614,216 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V78F) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00024 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00019 (0 hom.)
• Consequence: LSMEM2 NM_153215.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.210
• Publications: 3 publications found

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

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.011640638).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153215.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LSMEM2	NM_153215.3	MANE Select	c.232G>A	p.Val78Ile	missense	Exon 3 of 4	NP_694947.1	Q8N112
	LSMEM2	NM_001304385.2		c.229G>A	p.Val77Ile	missense	Exon 3 of 4	NP_001291314.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LSMEM2	ENST00000316436.4	TSL:1 MANE Select	c.232G>A	p.Val78Ile	missense	Exon 3 of 4	ENSP00000315081.3	Q8N112
	LSMEM2	ENST00000948603.1		c.250G>A	p.Val84Ile	missense	Exon 3 of 4	ENSP00000618662.1
	LSMEM2	ENST00000878856.1		c.229G>A	p.Val77Ile	missense	Exon 3 of 4	ENSP00000548915.1

Frequencies

GnomAD3 genomes AF: 0.000243 AC: 37 AN: 152236 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000723

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00144

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000162

Gnomad OTH AF: 0.000479

GnomAD2 exomes AF: 0.000175 AC: 44 AN: 250994 AF XY: 0.000155

Gnomad AFR exome AF: 0.0000615

Gnomad AMR exome AF: 0.000579

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000185

Gnomad OTH exome AF: 0.000327

GnomAD4 exome AF: 0.000194 AC: 284 AN: 1461862 Hom.: 0 Cov.: 32 AF XY: 0.000173 AC XY: 126 AN XY: 727238

African (AFR) AF: 0.000209 AC: 7 AN: 33480

American (AMR) AF: 0.000514 AC: 23 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53404

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.000218 AC: 242 AN: 1112006

Other (OTH) AF: 0.000199 AC: 12 AN: 60394

GnomAD4 genome AF: 0.000243 AC: 37 AN: 152354 Hom.: 0 Cov.: 33 AF XY: 0.000295 AC XY: 22 AN XY: 74504

African (AFR) AF: 0.0000721 AC: 3 AN: 41590

American (AMR) AF: 0.00144 AC: 22 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000162 AC: 11 AN: 68036

Other (OTH) AF: 0.000474 AC: 1 AN: 2110

Alfa AF: 0.000236 Hom.: 0

Bravo AF: 0.000355

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.0000824 AC: 10

EpiCase AF: 0.000382

EpiControl AF: 0.000237

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.082
BayesDel_addAF	Benign	-0.57	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	1.2
DANN	Benign	0.69
DEOGEN2	Benign	0.030	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.089	N
LIST_S2	Benign	0.48	T
M_CAP	Benign	0.0077	T
MetaRNN	Benign	0.012	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.075	N
PhyloP100		0.21
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-0.32	N
REVEL	Benign	0.0020
Sift	Benign	0.71	T
Sift4G	Benign	0.97	T
Polyphen		0.0050	B
Vest4		0.085
MVP		0.014
MPC		0.087
ClinPred		0.012	T
GERP RS		-1.1
Varity_R		0.021
gMVP		0.080
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs151106412; hg19: chr3-50324164; COSMIC: COSV57113737; COSMIC: COSV57113737;