Variant 15-99729449-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBS1_SupportingBS2

The NM_001284417.2(LYSMD4):c.565G>C(p.Glu189Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000545 in 1,614,188 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00043 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00056 ( 9 hom. )

Consequence

LYSMD4
NM_001284417.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.942

Variant links:

Genes affected

LYSMD4 (HGNC:26571): (LysM domain containing 4) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

LYSMD4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.037824273).

BS1

Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.000558 (815/1461846) while in subpopulation MID AF= 0.0224 (129/5768). AF 95% confidence interval is 0.0192. There are 9 homozygotes in gnomad4_exome. There are 429 alleles in male gnomad4_exome subpopulation. Median coverage is 77. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

BS2

High Homozygotes in GnomAdExome4 at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LYSMD4	NM_001284417.2 linkuse as main transcript	c.565G>C	p.Glu189Gln	missense_variant	3/3	ENST00000684762.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LYSMD4	ENST00000684762.1 linkuse as main transcript	c.565G>C	p.Glu189Gln	missense_variant	3/3		NM_001284417.2	P1	Q5XG99-1

Frequencies

GnomAD3 genomes

AF:

0.000427

AC:

AN:

152224

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000719

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.000829

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000573

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.000628

AC:

158

AN:

251420

Hom.:

AF XY:

0.000743

AC XY:

101

AN XY:

135880

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.00113

Gnomad ASJ exome

AF:

0.000199

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000784

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000686

Gnomad OTH exome

AF:

0.00228

GnomAD4 exome

AF:

0.000558

AC:

815

AN:

1461846

Hom.:

Cov.:

AF XY:

0.000590

AC XY:

429

AN XY:

727226

show subpopulations

Gnomad4 AFR exome

AF:

0.00108

Gnomad4 AMR exome

AF:

0.00121

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000974

Gnomad4 FIN exome

AF:

0.0000375

Gnomad4 NFE exome

AF:

0.000404

Gnomad4 OTH exome

AF:

0.00101

GnomAD4 genome

AF:

0.000427

AC:

AN:

152342

Hom.:

Cov.:

AF XY:

0.000430

AC XY:

AN XY:

74502

show subpopulations

Gnomad4 AFR

AF:

0.0000481

Gnomad4 AMR

AF:

0.000718

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.000830

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.000573

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.000653

Hom.:

Bravo

AF:

0.000412

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000544

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00142

EpiControl

AF:

0.00119

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

Jun 23, 2021

The c.568G>C (p.E190Q) alteration is located in exon 6 (coding exon 4) of the LYSMD4 gene. This alteration results from a G to C substitution at nucleotide position 568, causing the glutamic acid (E) at amino acid position 190 to be replaced by a glutamine (Q). 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

0.11

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.54

CADD

Benign

DANN

Uncertain

0.98

Eigen

Benign

-0.28

Eigen_PC

Benign

-0.37

FATHMM_MKL

Benign

0.45

LIST_S2

Benign

0.70

T;T;T;T

M_CAP

Benign

0.0052

MetaRNN

Benign

0.038

T;T;T;T

MetaSVM

Benign

-0.98

MutationTaster

Benign

0.93

D;D;D;N

PrimateAI

Benign

0.28

REVEL

Benign

0.11

Sift4G

Benign

0.090

T;T;T;T

Polyphen

0.33, 0.79

.;.;B;P

Vest4

0.055

MVP

0.29

MPC

0.32

ClinPred

0.026

GERP RS

4.2

Varity_R

0.12

gMVP

0.44

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