rs757147236

Variant names:

• chr15-99731790-G-A
• rs757147236
• ENST00000344791.6:c.122C>T

Your query was ambiguous. Multiple possible variants found:

• chr15-99731790-G-A
• chr15-99731790-G-C

Variant summary

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

The NM_001284421.2(LYSMD4):​c.-195C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000343 in 1,459,570 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: not found (cov: 33)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: LYSMD4 NM_001284421.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.889
• Publications: 1 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=0.055001765).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001284421.2. 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.210C>T	p.Asp70Asp	synonymous	Exon 2 of 3	NP_001271346.1	Q5XG99-1
	LYSMD4	NM_001284421.2		c.-195C>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 4	NP_001271350.1	B3KWE4
	LYSMD4	NM_001284422.2		c.-195C>T		5_prime_UTR_premature_start_codon_gain	Exon 3 of 5	NP_001271351.1	B3KWE4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LYSMD4	ENST00000344791.6	TSL:1	c.122C>T	p.Thr41Met	missense	Exon 3 of 6	ENSP00000342840.2	Q5XG99-2
	LYSMD4	ENST00000684762.1	MANE Select	c.210C>T	p.Asp70Asp	synonymous	Exon 2 of 3	ENSP00000506747.1	Q5XG99-1
	LYSMD4	ENST00000409796.5	TSL:1	c.210C>T	p.Asp70Asp	synonymous	Exon 2 of 3	ENSP00000386283.1	Q5XG99-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000399 AC: 1 AN: 250362 AF XY: 0.00000738

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000343 AC: 5 AN: 1459570 Hom.: 0 Cov.: 32 AF XY: 0.00000551 AC XY: 4 AN XY: 726056

African (AFR) AF: 0.00 AC: 0 AN: 33418

American (AMR) AF: 0.00 AC: 0 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.0000348 AC: 3 AN: 86152

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53086

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4350

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111788

Other (OTH) AF: 0.00 AC: 0 AN: 60234

GnomAD4 genome Cov.: 33

ExAC AF: 0.00000824 AC: 1

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	0.14
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	3.0
DANN	Benign	0.87
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.054	N
LIST_S2	Benign	0.47	T
M_CAP	Benign	0.0052	T
MetaRNN	Benign	0.055	T
MetaSVM	Benign	-1.0	T
PhyloP100		-0.89
PrimateAI	Benign	0.34	T
PROVEAN	Benign	0.25	N
REVEL	Benign	0.015
Sift	Benign	0.22	T
Sift4G	Pathogenic	0.0	D
Polyphen		0.41	B
Vest4		0.14
MutPred		0.40		Gain of catalytic residue at T41 (P = 8e-04)
MVP		0.030
MPC		0.15
ClinPred		0.095	T
GERP RS		-4.9
gMVP		0.26

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: rs757147236; hg19: chr15-100271995;