Genetic Variant LYSMD4:p.Asp70Glu (chr15-99731790-G-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001284417.2(LYSMD4):c.210C>G(p.Asp70Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000411 in 1,459,570 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. D70D) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

LYSMD4
NM_001284417.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.889

Publications

1 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.060511023).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001284417.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LYSMD4	NM_001284417.2	MANE Select	c.210C>G	p.Asp70Glu	missense	Exon 2 of 3	NP_001271346.1	Q5XG99-1
LYSMD4	NM_152449.4		c.122C>G	p.Thr41Arg	missense	Exon 3 of 6	NP_689662.2
LYSMD4	NM_001284418.2		c.210C>G	p.Asp70Glu	missense	Exon 2 of 3	NP_001271347.1	Q5XG99-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LYSMD4	ENST00000684762.1	MANE Select	c.210C>G	p.Asp70Glu	missense	Exon 2 of 3	ENSP00000506747.1	Q5XG99-1
LYSMD4	ENST00000344791.6	TSL:1	c.122C>G	p.Thr41Arg	missense	Exon 3 of 6	ENSP00000342840.2	Q5XG99-2
LYSMD4	ENST00000409796.5	TSL:1	c.210C>G	p.Asp70Glu	missense	Exon 2 of 3	ENSP00000386283.1	Q5XG99-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000799

AC:

AN:

250362

AF XY:

0.00000738

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.00000411

AC:

AN:

1459570

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726056

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33418

American (AMR)

AF:

0.0000224

AC:

AN:

44712

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26132

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86152

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53086

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4350

European-Non Finnish (NFE)

AF:

0.00000180

AC:

AN:

1111788

Other (OTH)

AF:

0.0000332

AC:

AN:

60234

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000508

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.75

CADD

Benign

2.8

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.047

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.19

LIST_S2

Benign

0.44

M_CAP

Benign

0.0024

MetaRNN

Benign

0.061

MetaSVM

Benign

-1.0

MutationAssessor

Benign

2.0

PhyloP100

-0.89

PROVEAN

Uncertain

-2.5

REVEL

Benign

0.0070

Sift

Benign

0.088

Sift4G

Benign

0.18

Polyphen

0.052

Vest4

0.071

MutPred

0.33

Gain of catalytic residue at D70 (P = 0.081)

MVP

0.081

ClinPred

0.34

GERP RS

-4.9

Varity_R

0.10

Mutation Taster

=93/7

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.17

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over