Variant 5-90525259-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The ENST00000315948.11(LYSMD3):c.31C>T(p.Pro11Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000219 in 1,458,042 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000022 ( 0 hom. )

Consequence

LYSMD3
ENST00000315948.11 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.47

Variant links:

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]

LYSMD3 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LYSMD3	NM_198273.2 linkuse as main transcript	c.31C>T	p.Pro11Ser	missense_variant	2/3	ENST00000315948.11	NP_938014.1	Q7Z3D4-1A8K613
LYSMD3	NM_001286812.1 linkuse as main transcript	c.31C>T	p.Pro11Ser	missense_variant	2/3		NP_001273741.1	Q7Z3D4-2
LYSMD3	XM_047416694.1 linkuse as main transcript	c.31C>T	p.Pro11Ser	missense_variant	2/3		XP_047272650.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
LYSMD3	ENST00000315948.11 linkuse as main transcript	c.31C>T	p.Pro11Ser	missense_variant	2/3	1	NM_198273.2	ENSP00000314518.6	Q7Z3D4-1
LYSMD3	ENST00000500869.6 linkuse as main transcript	c.31C>T	p.Pro11Ser	missense_variant	3/4	1		ENSP00000427020.1	Q7Z3D4-3
LYSMD3	ENST00000509384.5 linkuse as main transcript	c.31C>T	p.Pro11Ser	missense_variant	2/3	1		ENSP00000427683.1	Q7Z3D4-2
LYSMD3	ENST00000453259.2 linkuse as main transcript	n.31C>T		non_coding_transcript_exon_variant	2/4	3		ENSP00000405507.2	G5E9N8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000124

AC:

AN:

242768

Hom.:

AF XY:

0.00000758

AC XY:

AN XY:

131864

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000273

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000219

AC:

AN:

1458042

Hom.:

Cov.:

AF XY:

0.0000234

AC XY:

AN XY:

725106

show subpopulations

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:

0.0000117

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000270

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000248

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 06, 2023

The c.31C>T (p.P11S) alteration is located in exon 2 (coding exon 1) of the LYSMD3 gene. This alteration results from a C to T substitution at nucleotide position 31, causing the proline (P) at amino acid position 11 to be replaced by a serine (S). 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

0.067

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.56

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.011

.;T;.

Eigen

Benign

-0.46

Eigen_PC

Benign

-0.19

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.62

T;T;T

M_CAP

Benign

0.0031

MetaRNN

Benign

0.039

T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

-0.20

N;N;N

MutationTaster

Benign

0.99

N;N;N;N

PrimateAI

Benign

0.32

PROVEAN

Benign

-0.83

N;N;N

REVEL

Benign

0.035

Sift

Benign

0.084

T;T;T

Sift4G

Benign

0.66

T;T;T

Polyphen

0.023

B;B;B

Vest4

0.15

MutPred

0.17

Gain of MoRF binding (P = 0.0334);Gain of MoRF binding (P = 0.0334);Gain of MoRF binding (P = 0.0334);

MVP

0.068

MPC

0.13

ClinPred

0.086

GERP RS

4.9

Varity_R

0.036

gMVP

0.54

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.38

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.38

Position offset: -10

DS_AL_spliceai

0.30

Position offset: 41

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over