chr7-112489813-A-C

Variant names:

• chr7-112489813-A-C
• rs746667389
• NM_182597.3:c.260A>C

Variant summary

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

The NM_182597.3(LSMEM1):​c.260A>C​(p.Gln87Pro) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,458,852 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. Q87R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: LSMEM1 NM_182597.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.48
• Publications: 0 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.260A>C	p.Gln87Pro	missense	Exon 4 of 4	NP_872403.1	Q8N8F7-1
	LSMEM1	NM_001134468.2		c.260A>C	p.Gln87Pro	missense	Exon 4 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.260A>C	p.Gln87Pro	missense	Exon 4 of 4	ENSP00000323304.3	Q8N8F7-1
	ENSG00000288640	ENST00000676282.1		n.*422A>C		non_coding_transcript_exon	Exon 15 of 15	ENSP00000501830.1
	ENSG00000288640	ENST00000676282.1		n.*422A>C		3_prime_UTR	Exon 15 of 15	ENSP00000501830.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1458852 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 725710

African (AFR) AF: 0.00 AC: 0 AN: 33266

American (AMR) AF: 0.00 AC: 0 AN: 43990

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25928

East Asian (EAS) AF: 0.00 AC: 0 AN: 39662

South Asian (SAS) AF: 0.00 AC: 0 AN: 85590

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53354

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5740

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111088

Other (OTH) AF: 0.00 AC: 0 AN: 60234

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.59
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.020
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.37	T
Eigen	Uncertain	0.57
Eigen_PC	Uncertain	0.60
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.77	T
M_CAP	Benign	0.011	T
MetaRNN	Uncertain	0.70	D
MetaSVM	Benign	-0.53	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		5.5
PrimateAI	Benign	0.47	T
PROVEAN	Pathogenic	-5.3	D
REVEL	Benign	0.23
Sift	Uncertain	0.0080	D
Sift4G	Uncertain	0.013	D
Polyphen		1.0	D
Vest4		0.76
MutPred		0.36		Loss of sheet (P = 0.0315)
MVP		0.23
MPC		0.29
ClinPred		0.99	D
GERP RS		5.7
Varity_R		0.89
gMVP		0.77
Mutation Taster		=75/25	polymorphism

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

Other links and lift over

dbSNP: rs746667389; hg19: chr7-112129868;