chr15-99731827-C-A

Variant names:

• chr15-99731827-C-A
• rs1475130359
• NM_001284417.2:c.173G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001284417.2(LYSMD4):​c.173G>T​(p.Ser58Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,460,574 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: LYSMD4 NM_001284417.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.00600
• Publications: 0 publications found

Genes affected

LYSMD4 (HGNC:26571): (LysM domain containing 4) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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=0.035928756).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001284417.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LYSMD4	NM_001284417.2	MANE Select	c.173G>T	p.Ser58Ile	missense	Exon 2 of 3	NP_001271346.1	Q5XG99-1
	LYSMD4	NM_152449.4		c.85G>T	p.Ala29Ser	missense	Exon 3 of 6	NP_689662.2
	LYSMD4	NM_001284418.2		c.173G>T	p.Ser58Ile	missense	Exon 2 of 3	NP_001271347.1	Q5XG99-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LYSMD4	ENST00000684762.1	MANE Select	c.173G>T	p.Ser58Ile	missense	Exon 2 of 3	ENSP00000506747.1	Q5XG99-1
	LYSMD4	ENST00000344791.6	TSL:1	c.85G>T	p.Ala29Ser	missense	Exon 3 of 6	ENSP00000342840.2	Q5XG99-2
	LYSMD4	ENST00000409796.5	TSL:1	c.173G>T	p.Ser58Ile	missense	Exon 2 of 3	ENSP00000386283.1	Q5XG99-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1460574 Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2 AN XY: 726582

African (AFR) AF: 0.00 AC: 0 AN: 33446

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86214

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53076

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4980

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1112002

Other (OTH) AF: 0.00 AC: 0 AN: 60296

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	6.5
DANN	Benign	0.73
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.074	N
LIST_S2	Benign	0.42	T
M_CAP	Benign	0.0043	T
MetaRNN	Benign	0.036	T
MetaSVM	Benign	-0.99	T
PhyloP100		0.0060
PrimateAI	Benign	0.26	T
PROVEAN	Benign	0.28	N
REVEL	Benign	0.045
Sift	Benign	0.64	T
Sift4G	Pathogenic	0.0	D
Polyphen		0.62	P
Vest4		0.12
MutPred		0.30		Loss of helix (P = 0.0123)
MVP		0.014
MPC		0.13
ClinPred		0.044	T
GERP RS		-6.2
Varity_R		0.083
gMVP		0.16
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs1475130359; hg19: chr15-100272032;