LSMEM1 p.Ser74Arg

Variant names:

• chr7-112487015-A-C
• NM_182597.3:c.220A>C
• LSMEM1 p.Ser74Arg

Your query was ambiguous. Multiple possible variants found:

• chr7-112487015-A-C
• chr7-112487017-C-A
• chr7-112487017-C-G
• chr7-112487015-AGC-CGT
• chr7-112487015-AGC-CGA
• chr7-112487015-AGC-CGG

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_182597.3(LSMEM1):​c.220A>C​(p.Ser74Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: LSMEM1 NM_182597.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.70
• 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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.774

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.220A>C	p.Ser74Arg	missense	Exon 3 of 4	NP_872403.1	Q8N8F7-1
	LSMEM1	NM_001134468.2		c.220A>C	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.220A>C	p.Ser74Arg	missense	Exon 3 of 4	ENSP00000323304.3	Q8N8F7-1
	ENSG00000288640	ENST00000676282.1		n.*382A>C		non_coding_transcript_exon	Exon 14 of 15	ENSP00000501830.1
	ENSG00000288640	ENST00000676282.1		n.*382A>C		3_prime_UTR	Exon 14 of 15	ENSP00000501830.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Uncertain	0.040
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.32	T
Eigen	Uncertain	0.31
Eigen_PC	Uncertain	0.30
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.0075	T
MetaRNN	Pathogenic	0.77	D
MetaSVM	Benign	-0.83	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		3.7
PrimateAI	Uncertain	0.61	T
PROVEAN	Uncertain	-4.1	D
REVEL	Benign	0.28
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.0080	D
Varity_R		0.87
gMVP		0.70
Mutation Taster		=89/11	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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr7-112127070;