chr15-99729529-T-G

Variant names:

• chr15-99729529-T-G
• rs878919102
• NM_001284417.2:c.485A>C

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.485A>C​(p.Gln162Pro) 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)
  • Exomes 𝑓: 0.0000069 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: LYSMD4 NM_001284417.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0850
• 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=0.061887264).

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.485A>C	p.Gln162Pro	missense	Exon 3 of 3	NP_001271346.1	Q5XG99-1
	LYSMD4	NM_152449.4		c.488A>C	p.Gln163Pro	missense	Exon 6 of 6	NP_689662.2
	LYSMD4	NM_001284418.2		c.485A>C	p.Gln162Pro	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.485A>C	p.Gln162Pro	missense	Exon 3 of 3	ENSP00000506747.1	Q5XG99-1
	LYSMD4	ENST00000344791.6	TSL:1	c.488A>C	p.Gln163Pro	missense	Exon 6 of 6	ENSP00000342840.2	Q5XG99-2
	LYSMD4	ENST00000409796.5	TSL:1	c.485A>C	p.Gln162Pro	missense	Exon 3 of 3	ENSP00000386283.1	Q5XG99-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000689 AC: 10 AN: 1452220 Hom.: 0 Cov.: 35 AF XY: 0.00000553 AC XY: 4 AN XY: 722880

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 33174

American (AMR) AF: 0.00 AC: 0 AN: 44482

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25606

East Asian (EAS) AF: 0.0000257 AC: 1 AN: 38948

South Asian (SAS) AF: 0.00 AC: 0 AN: 86168

European-Finnish (FIN) AF: 0.0000767 AC: 4 AN: 52172

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5712

European-Non Finnish (NFE) AF: 0.00000362 AC: 4 AN: 1106292

Other (OTH) AF: 0.0000168 AC: 1 AN: 59666

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

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	0.051
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	1.3
DANN	Benign	0.18
DEOGEN2	Benign	0.010	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.38	T
M_CAP	Benign	0.0024	T
MetaRNN	Benign	0.062	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.71	N
PhyloP100		-0.085
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-1.0	N
REVEL	Benign	0.088
Sift	Benign	0.32	T
Sift4G	Benign	0.30	T
Polyphen		0.0010	B
Vest4		0.086
MutPred		0.45		Loss of helix (P = 0.0068)
MVP		0.040
MPC		0.17
ClinPred		0.077	T
GERP RS		-3.5
Varity_R		0.093
gMVP		0.45
Mutation Taster		=74/26	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: rs878919102; hg19: chr15-100269734;