chr15-99729539-T-C

Variant names:

• chr15-99729539-T-C
• NM_001284417.2:c.475A>G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001284417.2(LYSMD4):​c.475A>G​(p.Thr159Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,457,138 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: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: LYSMD4 NM_001284417.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.81

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

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=0.03767699).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LYSMD4	NM_001284417.2	c.475A>G	p.Thr159Ala	missense_variant	Exon 3 of 3	ENST00000684762.1	NP_001271346.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LYSMD4	ENST00000684762.1	c.475A>G	p.Thr159Ala	missense_variant	Exon 3 of 3		NM_001284417.2	ENSP00000506747.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1457138 Hom.: 0 Cov.: 35 AF XY: 0.00 AC XY: 0 AN XY: 725134

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: 9.02e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.062
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.036
DANN	Benign	0.24
DEOGEN2	Benign	0.0023	.;T;T;.
Eigen	Benign	-1.9
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.017	N
LIST_S2	Benign	0.35	T;T;T;T
M_CAP	Benign	0.0030	T
MetaRNN	Benign	0.038	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-1.0	.;.;N;.
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-0.070	.;.;N;N
REVEL	Benign	0.0030
Sift	Benign	0.71	.;.;T;T
Sift4G	Benign	0.57	T;T;T;T
Polyphen		0.0, 0.015	.;.;B;B
Vest4		0.021
MutPred		0.45		.;.;Loss of phosphorylation at T159 (P = 0.0504);.;
MVP		0.040
MPC		0.14
ClinPred		0.021	T
GERP RS		-2.9
Varity_R		0.023
gMVP		0.31

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr15-100269744; COSMIC: COSV100230550; COSMIC: COSV100230550;