Variant 1-151160976-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_212551.5(LYSMD1):c.590T>C(p.Met197Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000558 in 1,614,084 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 31)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

LYSMD1
NM_212551.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.227

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 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=0.01367861).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LYSMD1	NM_212551.5 linkuse as main transcript	c.590T>C	p.Met197Thr	missense_variant	3/3	ENST00000368908.10	NP_997716.1	Q96S90-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
LYSMD1	ENST00000368908.10 linkuse as main transcript	c.590T>C	p.Met197Thr	missense_variant	3/3	1	NM_212551.5	ENSP00000357904.5	Q96S90-1
LYSMD1	ENST00000440902.2 linkuse as main transcript	c.446T>C	p.Met149Thr	missense_variant	3/3	2		ENSP00000404059.2	Q96S90-2
SCNM1	ENST00000602841.5 linkuse as main transcript	c.-55+4254A>G		intron_variant		3		ENSP00000473282.1	Q9BWG6-2

Frequencies

GnomAD3 genomes

AF:

0.0000526

AC:

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000193

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000796

AC:

AN:

251152

Hom.:

AF XY:

0.00000737

AC XY:

AN XY:

135766

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS 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:

6.84e-7

AC:

AN:

1461872

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727244

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000526

AC:

AN:

152212

Hom.:

Cov.:

AF XY:

0.0000807

AC XY:

AN XY:

74364

show subpopulations

Gnomad4 AFR

AF:

0.000193

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000416

ExAC

AF:

0.0000165

AC:

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

Aug 05, 2024

The c.590T>C (p.M197T) alteration is located in exon 3 (coding exon 3) of the LYSMD1 gene. This alteration results from a T to C substitution at nucleotide position 590, causing the methionine (M) at amino acid position 197 to be replaced by a threonine (T). 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

0.12

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.64

CADD

Benign

6.2

DANN

Benign

0.63

DEOGEN2

Benign

0.0050

T;.

Eigen

Benign

-0.98

Eigen_PC

Benign

-0.83

FATHMM_MKL

Benign

0.018

LIST_S2

Benign

0.42

T;T

M_CAP

Benign

0.0015

MetaRNN

Benign

0.014

T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.035

N;.

PrimateAI

Benign

0.45

PROVEAN

Benign

0.14

N;N

REVEL

Benign

0.019

Sift

Benign

1.0

T;T

Sift4G

Benign

0.72

T;T

Polyphen

0.0

B;B

Vest4

0.074

MutPred

0.25

Gain of phosphorylation at M197 (P = 0.069);.;

MVP

0.081

MPC

0.33

ClinPred

0.015

GERP RS

0.23

Varity_R

0.014

gMVP

0.20

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

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