chr7-112487017-C-A

Variant names:

• chr7-112487017-C-A
• rs544127044
• NM_182597.3:c.222C>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_182597.3(LSMEM1):​c.222C>A​(p.Ser74Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000044 in 1,614,100 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000047 (0 hom.)
• Consequence: LSMEM1 NM_182597.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.637
• Publications: 4 publications found

Genes affected

LSMEM1 (HGNC:22036): (leucine rich single-pass membrane protein 1) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000288640 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_182597.3. 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
	LSMEM1	NM_182597.3	MANE Select	c.222C>A	p.Ser74Arg	missense	Exon 3 of 4	NP_872403.1	Q8N8F7-1
	LSMEM1	NM_001134468.2		c.222C>A	p.Ser74Arg	missense	Exon 3 of 4	NP_001127940.1	Q8N8F7-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LSMEM1	ENST00000312849.4	TSL:1 MANE Select	c.222C>A	p.Ser74Arg	missense	Exon 3 of 4	ENSP00000323304.3	Q8N8F7-1
	ENSG00000288640	ENST00000676282.1		n.*384C>A		non_coding_transcript_exon	Exon 14 of 15	ENSP00000501830.1
	ENSG00000288640	ENST00000676282.1		n.*384C>A		3_prime_UTR	Exon 14 of 15	ENSP00000501830.1

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152154 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000441

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000199 AC: 5 AN: 251440 AF XY: 0.0000147

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000440

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000465 AC: 68 AN: 1461828 Hom.: 0 Cov.: 30 AF XY: 0.0000413 AC XY: 30 AN XY: 727218

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.0000224 AC: 1 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53410

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

European-Non Finnish (NFE) AF: 0.0000567 AC: 63 AN: 1111970

Other (OTH) AF: 0.0000662 AC: 4 AN: 60388

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152272 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74466

African (AFR) AF: 0.00 AC: 0 AN: 41542

American (AMR) AF: 0.00 AC: 0 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

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

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68024

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.0000564 Hom.: 0

Bravo AF: 0.0000227

ExAC AF: 0.0000330 AC: 4

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Uncertain	0.072	D
BayesDel_noAF	Uncertain	0.0
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.32	T
Eigen	Uncertain	0.29
Eigen_PC	Uncertain	0.27
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.0063	T
MetaRNN	Uncertain	0.66	D
MetaSVM	Benign	-0.78	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		0.64
PrimateAI	Uncertain	0.61	T
PROVEAN	Uncertain	-4.1	D
REVEL	Uncertain	0.35
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.0080	D
Polyphen		0.99	D
Vest4		0.74
MutPred		0.61		Loss of catalytic residue at S74 (P = 0.089)
MVP		0.22
MPC		0.25
ClinPred		0.93	D
GERP RS		4.1
Varity_R		0.86
gMVP		0.70
Mutation Taster		=89/11	polymorphism

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

Other links and lift over

dbSNP: rs544127044; hg19: chr7-112127072; COSMIC: COSV57196776;