NM_001199050.2:c.232A>G

Variant names:

• chr1-205416270-T-C
• NM_001199050.2:c.232A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001199050.2(LEMD1):​c.232A>G​(p.Ile78Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: LEMD1 NM_001199050.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.156
• Publications: 0 publications found

Genes affected

LEMD1 (HGNC:18725): (LEM domain containing 1) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

LEMD1-AS1 (HGNC:44132): (LEMD1 antisense RNA 1)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.046302736).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001199050.2. 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
	LEMD1	NM_001199050.2	MANE Select	c.232A>G	p.Ile78Val	missense	Exon 4 of 6	NP_001185979.1	Q68G75-1
	LEMD1	NM_001199051.2		c.109A>G	p.Ile37Val	missense	Exon 3 of 5	NP_001185980.1	Q68G75-3
	LEMD1	NM_001001552.5		c.205+2960A>G		intron	N/A	NP_001001552.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LEMD1	ENST00000367153.9	TSL:1 MANE Select	c.232A>G	p.Ile78Val	missense	Exon 4 of 6	ENSP00000356121.4	Q68G75-1
	LEMD1	ENST00000367151.4	TSL:1	c.232A>G	p.Ile78Val	missense	Exon 3 of 5	ENSP00000356119.3	Q68G75-1
	LEMD1	ENST00000476884.1	TSL:1	n.161+4185A>G		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

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	Benign	0.10
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	10
DANN	Benign	0.86
DEOGEN2	Benign	0.000092	T
Eigen	Benign	-0.25
Eigen_PC	Benign	-0.18
FATHMM_MKL	Benign	0.47	N
LIST_S2	Benign	0.44	T
M_CAP	Benign	0.0044	T
MetaRNN	Benign	0.046	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.90	L
PhyloP100		0.16
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-0.69	N
REVEL	Benign	0.029
Sift	Benign	0.049	D
Sift4G	Benign	0.10	T
Polyphen		0.52	P
Vest4		0.050
MutPred		0.27		Gain of loop (P = 0.0111)
MVP		0.072
MPC		0.027
ClinPred		0.12	T
GERP RS		2.3
Varity_R		0.044
gMVP		0.061
Mutation Taster		=96/4	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

hg19: chr1-205385398;