Variant 5-90519385-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_198273.2(LYSMD3):c.355G>A(p.Glu119Lys) variant causes a missense change. The variant allele was found at a frequency of 0.0000644 in 1,613,766 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000092 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000062 ( 0 hom. )

Consequence

LYSMD3
NM_198273.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.77

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
LYSMD3	NM_198273.2 linkuse as main transcript	c.355G>A	p.Glu119Lys	missense_variant	3/3	ENST00000315948.11	NP_938014.1
LYSMD3	NM_001286812.1 linkuse as main transcript	c.296G>A	p.Arg99Gln	missense_variant	3/3		NP_001273741.1
LYSMD3	XM_047416694.1 linkuse as main transcript	c.*1059G>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 linkuse as main transcript	c.355G>A	p.Glu119Lys	missense_variant	3/3	1	NM_198273.2	ENSP00000314518	P1	Q7Z3D4-1
LYSMD3	ENST00000509384.5 linkuse as main transcript	c.296G>A	p.Arg99Gln	missense_variant	3/3	1		ENSP00000427683		Q7Z3D4-2
LYSMD3	ENST00000500869.6 linkuse as main transcript	c.256-376G>A		intron_variant		1		ENSP00000427020		Q7Z3D4-3
LYSMD3	ENST00000453259.2 linkuse as main transcript			downstream_gene_variant		3		ENSP00000405507

Frequencies

GnomAD3 genomes

AF:

0.0000921

AC:

AN:

151968

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000883

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000601

AC:

AN:

249416

Hom.:

AF XY:

0.0000517

AC XY:

AN XY:

135324

show subpopulations

Gnomad AFR exome

AF:

0.000194

Gnomad AMR exome

AF:

0.0000580

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000556

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000707

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000616

AC:

AN:

1461798

Hom.:

Cov.:

AF XY:

0.0000591

AC XY:

AN XY:

727198

show subpopulations

Gnomad4 AFR exome

AF:

0.000149

Gnomad4 AMR exome

AF:

0.0000447

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000692

Gnomad4 OTH exome

AF:

0.0000828

GnomAD4 genome

AF:

0.0000921

AC:

AN:

151968

Hom.:

Cov.:

AF XY:

0.0000808

AC XY:

AN XY:

74228

show subpopulations

Gnomad4 AFR

AF:

0.000169

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000883

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000773

Hom.:

Bravo

AF:

0.0000982

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.000542

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000579

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.0000593

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

Aug 16, 2021

The c.355G>A (p.E119K) 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 355, causing the glutamic acid (E) at amino acid position 119 to be replaced by a lysine (K). 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

Uncertain

0.45

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.20

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.26

Eigen

Uncertain

0.36

Eigen_PC

Uncertain

0.48

FATHMM_MKL

Uncertain

0.82

LIST_S2

Uncertain

0.90

M_CAP

Benign

0.060

MetaRNN

Uncertain

0.73

MetaSVM

Benign

-0.59

MutationTaster

Benign

1.0

D;D;D;N

PrimateAI

Uncertain

0.62

PROVEAN

Uncertain

-3.0

REVEL

Benign

0.17

Sift

Uncertain

0.0030

Sift4G

Uncertain

0.0070

Polyphen

1.0

Vest4

0.86

MVP

0.22

MPC

0.58

ClinPred

0.48

GERP RS

5.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.51

gMVP

0.72

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

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