chr15-99729184-G-C

Variant names:

• chr15-99729184-G-C
• NM_001284417.2:c.830C>G

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.830C>G​(p.Ala277Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 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)
• Consequence: LYSMD4 NM_001284417.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.920
• 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=0.06059712).

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.830C>G	p.Ala277Gly	missense	Exon 3 of 3	NP_001271346.1	Q5XG99-1
	LYSMD4	NM_152449.4		c.833C>G	p.Ala278Gly	missense	Exon 6 of 6	NP_689662.2
	LYSMD4	NM_001284418.2		c.830C>G	p.Ala277Gly	missense	Exon 3 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.830C>G	p.Ala277Gly	missense	Exon 3 of 3	ENSP00000506747.1	Q5XG99-1
	LYSMD4	ENST00000344791.6	TSL:1	c.833C>G	p.Ala278Gly	missense	Exon 6 of 6	ENSP00000342840.2	Q5XG99-2
	LYSMD4	ENST00000409796.5	TSL:1	c.830C>G	p.Ala277Gly	missense	Exon 3 of 3	ENSP00000386283.1	Q5XG99-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 77

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	-0.29	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	15
DANN	Benign	0.97
DEOGEN2	Benign	0.0052	T
Eigen	Benign	-0.74
Eigen_PC	Benign	-0.70
FATHMM_MKL	Benign	0.24	N
LIST_S2	Benign	0.70	T
M_CAP	Benign	0.0055	T
MetaRNN	Benign	0.061	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.92
PrimateAI	Benign	0.24	T
PROVEAN	Benign	0.15	N
REVEL	Benign	0.034
Sift	Benign	0.17	T
Sift4G	Benign	0.45	T
Polyphen		0.039	B
Vest4		0.075
MutPred		0.17		Gain of loop (P = 0.0502)
MVP		0.014
MPC		0.24
ClinPred		0.069	T
GERP RS		3.0
Varity_R		0.034
gMVP		0.32

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

hg19: chr15-100269389;