1-151162037-G-C

Position:

• chr1-151162037-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_212551.5(LYSMD1):​c.244C>G​(p.Leu82Val) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,460,976 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: LYSMD1 NM_212551.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.23

Genes affected

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

TNFAIP8L2-SCNM1 (HGNC:):

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.828

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LYSMD1	NM_212551.5	c.244C>G	p.Leu82Val	missense_variant	2/3	ENST00000368908.10	NP_997716.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LYSMD1	ENST00000368908.10	c.244C>G	p.Leu82Val	missense_variant	2/3	1	NM_212551.5	ENSP00000357904.5
LYSMD1	ENST00000440902.2	c.100C>G	p.Leu34Val	missense_variant	2/3	2		ENSP00000404059.2
SCNM1	ENST00000602841.5	c.-54-4434G>C		intron_variant		3		ENSP00000473282.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1460976 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 726838

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

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

May 23, 2023

The c.244C>G (p.L82V) alteration is located in exon 2 (coding exon 2) of the LYSMD1 gene. This alteration results from a C to G substitution at nucleotide position 244, causing the leucine (L) at amino acid position 82 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	0.15
BayesDel_addAF	Benign	0.0034	T
BayesDel_noAF	Benign	-0.23
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.080	T;.
Eigen	Uncertain	0.24
Eigen_PC	Uncertain	0.32
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.85	D;T
M_CAP	Benign	0.038	D
MetaRNN	Pathogenic	0.83	D;D
MetaSVM	Benign	-0.69	T
MutationAssessor	Uncertain	2.2	M;.
PrimateAI	Uncertain	0.57	T
PROVEAN	Uncertain	-2.5	D;D
REVEL	Uncertain	0.30
Sift	Benign	0.047	D;D
Sift4G	Uncertain	0.051	T;T
Polyphen		0.28	B;B
Vest4		0.59
MutPred		0.88		Gain of methylation at K79 (P = 0.076);.;
MVP		0.67
MPC		0.86
ClinPred		0.96	D
GERP RS		4.9
Varity_R		0.23
gMVP		0.81

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: chr1-151134513;