5-90518980-C-T

Position:

• chr5-90518980-C-T

Variant summary

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

The NM_198273.2(LYSMD3):​c.760G>A​(p.Val254Met) 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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: LYSMD3 NM_198273.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.24

Genes affected

LYSMD3 (HGNC:26969): (LysM domain containing 3) Involved in Golgi organization. Located in Golgi apparatus and plasma 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=0.06291965).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LYSMD3	NM_198273.2	c.760G>A	p.Val254Met	missense_variant	3/3	ENST00000315948.11	NP_938014.1
LYSMD3	NM_001286812.1	c.*317G>A		3_prime_UTR_variant	3/3		NP_001273741.1
LYSMD3	XM_047416694.1	c.*1464G>A		3_prime_UTR_variant	3/3		XP_047272650.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LYSMD3	ENST00000315948.11	c.760G>A	p.Val254Met	missense_variant	3/3	1	NM_198273.2	ENSP00000314518	P1
LYSMD3	ENST00000500869.6	c.285G>A	p.Gln95=	synonymous_variant	4/4	1		ENSP00000427020
LYSMD3	ENST00000509384.5	c.*317G>A		3_prime_UTR_variant	3/3	1		ENSP00000427683

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 14, 2023

The c.760G>A (p.V254M) alteration is located in exon 3 (coding exon 2) of the LYSMD3 gene. This alteration results from a G to A substitution at nucleotide position 760, causing the valine (V) at amino acid position 254 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.088
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	17
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0066	T
Eigen	Benign	-0.21
Eigen_PC	Benign	-0.0036
FATHMM_MKL	Benign	0.35	N
LIST_S2	Benign	0.77	T
M_CAP	Benign	0.0032	T
MetaRNN	Benign	0.063	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	2.0	M
MutationTaster	Benign	1.0	D;D;N;N
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-0.63	N
REVEL	Benign	0.033
Sift	Benign	0.19	T
Sift4G	Benign	0.27	T
Polyphen		0.0070	B
Vest4		0.11
MutPred		0.13		Loss of catalytic residue at V254 (P = 0.0089);
MVP		0.068
MPC		0.13
ClinPred		0.32	T
GERP RS		5.0
Varity_R		0.042
gMVP		0.33

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: chr5-89814797; COSMIC: COSV60057666; COSMIC: COSV60057666;