Variant 1-151165177-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_212551.5(LYSMD1):c.82G>A(p.Val28Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000434 in 1,614,192 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000045 ( 0 hom. )

Consequence

LYSMD1
NM_212551.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.19

Variant links:

Genes affected

LYSMD1 (HGNC:32070): (LysM domain containing 1) Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

LYSMD1 links:

TNFAIP8L2-SCNM1 (HGNC:):

TNFAIP8L2-SCNM1 links:

SCNM1 (HGNC:23136): (sodium channel modifier 1) SCNM1 is a zinc finger protein and putative splicing factor. In mice, Scnm1 modifies phenotypic expression of Scn8a (MIM 600702) mutations (Buchner et al., 2003 [PubMed 12920299]).[supplied by OMIM, Oct 2009]

SCNM1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LYSMD1	NM_212551.5 link	c.82G>A	p.Val28Met	missense_variant	1/3	ENST00000368908.10	NP_997716.1	Q96S90-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
LYSMD1	ENST00000368908.10 link	c.82G>A	p.Val28Met	missense_variant	1/3	1	NM_212551.5	ENSP00000357904.5	Q96S90-1
SCNM1	ENST00000602841.5 link	c.-54-1294C>T		intron_variant		3		ENSP00000473282.1	Q9BWG6-2
LYSMD1	ENST00000440902.2 link	c.36+570G>A		intron_variant		2		ENSP00000404059.2	Q96S90-2

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000829

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000915

AC:

AN:

251434

Hom.:

AF XY:

0.000110

AC XY:

AN XY:

135894

show subpopulations

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 SAS exome

AF:

0.000719

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.0000451

AC:

AN:

1461882

Hom.:

Cov.:

AF XY:

0.0000578

AC XY:

AN XY:

727244

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000730

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152310

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000829

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ExAC

AF:

0.0000494

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 07, 2023

The c.82G>A (p.V28M) alteration is located in exon 1 (coding exon 1) of the LYSMD1 gene. This alteration results from a G to A substitution at nucleotide position 82, causing the valine (V) at amino acid position 28 to be replaced by a methionine (M). 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

Uncertain

0.53

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.30

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.014

Eigen

Uncertain

0.45

Eigen_PC

Uncertain

0.48

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.84

M_CAP

Benign

0.012

MetaRNN

Benign

0.061

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.7

PrimateAI

Uncertain

0.65

PROVEAN

Benign

-0.59

REVEL

Benign

0.13

Sift

Uncertain

0.014

Sift4G

Uncertain

0.029

Polyphen

0.98

Vest4

0.13

MutPred

0.20

Gain of MoRF binding (P = 0.1059);

MVP

0.44

MPC

0.91

ClinPred

0.55

GERP RS

4.9

Varity_R

0.16

gMVP

0.61

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.28

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.28

Position offset: -22

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over