NM_153374.3:c.193G>A

Variant names:

• chr15-51737430-C-T
• rs1434439306
• NM_153374.3:c.193G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_153374.3(LYSMD2):​c.193G>A​(p.Gly65Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000279 in 1,433,420 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G65V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0000023 (0 hom.)
• Consequence: LYSMD2 NM_153374.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.227
• Publications: 0 publications found

Genes affected

LYSMD2 (HGNC:28571): (LysM domain containing 2)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12108448).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153374.3. 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
	LYSMD2	NM_153374.3	MANE Select	c.193G>A	p.Gly65Ser	missense	Exon 1 of 3	NP_699205.1	Q8IV50-1
	LYSMD2	NM_001143917.2		c.1-12309G>A		intron	N/A	NP_001137389.1	Q8IV50-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LYSMD2	ENST00000267838.7	TSL:1 MANE Select	c.193G>A	p.Gly65Ser	missense	Exon 1 of 3	ENSP00000267838.3	Q8IV50-1
	LYSMD2	ENST00000454181.6	TSL:1	c.1-12309G>A		intron	N/A	ENSP00000410424.2	Q8IV50-2
	LYSMD2	ENST00000875743.1		c.193G>A	p.Gly65Ser	missense	Exon 1 of 3	ENSP00000545802.1

Frequencies

GnomAD3 genomes AF: 0.00000659 AC: 1 AN: 151778 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000175 AC: 1 AN: 57216 AF XY: 0.0000298

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000930

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: 0.00000234 AC: 3 AN: 1281534 Hom.: 0 Cov.: 33 AF XY: 0.00000158 AC XY: 1 AN XY: 631042

African (AFR) AF: 0.00 AC: 0 AN: 25630

American (AMR) AF: 0.00 AC: 0 AN: 21258

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21668

East Asian (EAS) AF: 0.00 AC: 0 AN: 27294

South Asian (SAS) AF: 0.00 AC: 0 AN: 68156

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 31746

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3906

European-Non Finnish (NFE) AF: 0.00000194 AC: 2 AN: 1029304

Other (OTH) AF: 0.0000190 AC: 1 AN: 52572

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 151886 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 74274

African (AFR) AF: 0.00 AC: 0 AN: 41498

American (AMR) AF: 0.00 AC: 0 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5140

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10500

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67868

Other (OTH) AF: 0.00 AC: 0 AN: 2108

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions

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	0.10
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	19
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0044	T
Eigen	Benign	-0.58
Eigen_PC	Benign	-0.41
FATHMM_MKL	Benign	0.41	N
LIST_S2	Benign	0.49	T
M_CAP	Pathogenic	0.55	D
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.23
PrimateAI	Pathogenic	0.93	D
PROVEAN	Benign	0.14	N
REVEL	Benign	0.0090
Sift	Benign	0.50	T
Sift4G	Benign	0.18	T
Polyphen		0.0030	B
Vest4		0.10
MutPred		0.39		Loss of helix (P = 0.0138)
MVP		0.18
MPC		0.12
ClinPred		0.13	T
GERP RS		3.0
PromoterAI		0.0038	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.10
gMVP		0.48
Mutation Taster		=90/10	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: rs1434439306; hg19: chr15-52029627;