Genetic Variant NM_001199050.2:c.211A>G (chr1-205416291-T-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001199050.2(LEMD1):c.211A>G(p.Asn71Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000717 in 1,395,066 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N71T) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.2e-7 ( 0 hom. )

Consequence

LEMD1
NM_001199050.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.369

Publications

0 publications found

Variant links:

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 links:

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

LEMD1-AS1 links:

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ACMG classification

Classification was made for transcript

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=0.045534015).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LEMD1	NM_001199050.2	MANE Select	c.211A>G	p.Asn71Asp	missense	Exon 4 of 6	NP_001185979.1	Q68G75-1
LEMD1	NM_001199051.2		c.88A>G	p.Asn30Asp	missense	Exon 3 of 5	NP_001185980.1	Q68G75-3
LEMD1	NM_001001552.5		c.205+2939A>G		intron	N/A	NP_001001552.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LEMD1	ENST00000367153.9	TSL:1 MANE Select	c.211A>G	p.Asn71Asp	missense	Exon 4 of 6	ENSP00000356121.4	Q68G75-1
LEMD1	ENST00000367151.4	TSL:1	c.211A>G	p.Asn71Asp	missense	Exon 3 of 5	ENSP00000356119.3	Q68G75-1
LEMD1	ENST00000476884.1	TSL:1	n.161+4164A>G		intron	N/A

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

148404

AF XY:

0.00

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

7.17e-7

AC:

AN:

1395066

Hom.:

Cov.:

AF XY:

0.00000145

AC XY:

AN XY:

688234

show subpopulations

African (AFR)

AF:

0.0000317

AC:

AN:

31502

American (AMR)

AF:

0.00

AC:

AN:

35580

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25154

East Asian (EAS)

AF:

0.00

AC:

AN:

35706

South Asian (SAS)

AF:

0.00

AC:

AN:

78982

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48028

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5684

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1076558

Other (OTH)

AF:

0.00

AC:

AN:

57872

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.090

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.71

CADD

Benign

(source)

DANN

Benign

0.94

DEOGEN2

Benign

0.0014

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.94

FATHMM_MKL

Benign

0.032

LIST_S2

Benign

0.36

M_CAP

Benign

0.0045

MetaRNN

Benign

0.046

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.55

PhyloP100

0.37

PrimateAI

Benign

0.41

PROVEAN

Benign

-1.2

REVEL

Benign

0.012

Sift

Benign

0.18

Sift4G

Benign

0.18

Polyphen

0.0060

Vest4

0.19

MutPred

0.27

Loss of loop (P = 0.0112)

MVP

0.061

MPC

0.029

ClinPred

0.027

GERP RS

2.4

Varity_R

0.065

gMVP

0.098

Mutation Taster

=97/3

polymorphism

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over