1-205416270-T-C

Position:

• chr1-205416270-T-C

Variant summary

Our verdict is Likely benign. Variant got -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. 15/21 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

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 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LEMD1	NM_001199050.2	c.232A>G	p.Ile78Val	missense_variant	4/6	ENST00000367153.9	NP_001185979.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LEMD1	ENST00000367153.9	c.232A>G	p.Ile78Val	missense_variant	4/6	1	NM_001199050.2	ENSP00000356121.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 02, 2021

The c.232A>G (p.I78V) alteration is located in exon 4 (coding exon 3) of the LEMD1 gene. This alteration results from a A to G substitution at nucleotide position 232, causing the isoleucine (I) at amino acid position 78 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

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;T
Eigen	Benign	-0.25
Eigen_PC	Benign	-0.18
FATHMM_MKL	Benign	0.47	N
LIST_S2	Benign	0.44	T;.;T
M_CAP	Benign	0.0044	T
MetaRNN	Benign	0.046	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.90	.;L;L
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-0.69	N;N;.
REVEL	Benign	0.029
Sift	Benign	0.049	D;D;.
Sift4G	Benign	0.10	T;T;T
Polyphen		0.52	P;B;B
Vest4		0.050
MutPred		0.27		.;Gain of loop (P = 0.0111);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

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-205385398;