chr1-205381729-C-T

Variant names:

• chr1-205381729-C-T
• NM_001199050.2:c.475G>A

Variant summary

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

The NM_001199050.2(LEMD1):​c.475G>A​(p.Ala159Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 3.18
• 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: 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_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.475G>A	p.Ala159Thr	missense	Exon 6 of 6	NP_001185979.1	Q68G75-1
	LEMD1	NM_001199051.2		c.352G>A	p.Ala118Thr	missense	Exon 5 of 5	NP_001185980.1	Q68G75-3
	LEMD1	NM_001001552.5		c.*6G>A		3_prime_UTR	Exon 4 of 4	NP_001001552.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LEMD1	ENST00000367153.9	TSL:1 MANE Select	c.475G>A	p.Ala159Thr	missense	Exon 6 of 6	ENSP00000356121.4	Q68G75-1
	LEMD1	ENST00000367151.4	TSL:1	c.475G>A	p.Ala159Thr	missense	Exon 5 of 5	ENSP00000356119.3	Q68G75-1
	LEMD1	ENST00000476884.1	TSL:1	n.366G>A		non_coding_transcript_exon	Exon 4 of 4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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	Uncertain	0.42
BayesDel_addAF	Benign	-0.031	T
BayesDel_noAF	Benign	-0.28
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0071	T
Eigen	Uncertain	0.33
Eigen_PC	Uncertain	0.27
FATHMM_MKL	Benign	0.62	D
LIST_S2	Benign	0.72	T
M_CAP	Benign	0.015	T
MetaRNN	Uncertain	0.54	D
MetaSVM	Benign	-0.74	T
MutationAssessor	Benign	1.0	L
PhyloP100		3.2
PrimateAI	Uncertain	0.50	T
PROVEAN	Uncertain	-2.5	D
REVEL	Benign	0.23
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.72
MutPred		0.37		Gain of sheet (P = 0.0125)
MVP		0.11
MPC		0.082
ClinPred		0.96	D
GERP RS		4.9
Varity_R		0.21
gMVP		0.21
Mutation Taster		=95/5	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

hg19: chr1-205350857;