Variant rs12773592 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001142308.3(MALRD1):c.4538A>G(p.Asp1513Gly) variant causes a missense change. The variant allele was found at a frequency of 0.136 in 1,549,940 control chromosomes in the GnomAD database, including 15,268 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.12 ( 1091 hom., cov: 31)

Exomes 𝑓: 0.14 ( 14177 hom. )

Consequence

MALRD1
NM_001142308.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.60

Variant links:

Genes affected

MALRD1 (HGNC:24331): (MAM and LDL receptor class A domain containing 1) This gene encodes a conserved protein that features multiple MAM (meprin-A5-protein tyrosine phosphatase mu) and LDLR A2 (low density lipoprotein receptor A2) domains. Expression of this gene is enriched in the small intestine and is upregulated during differentiation of a human cell line that exhibits properties of intestinal epithelial cells. The encoded protein has been shown to modulate production of FGF19 in a human intestinal cell line and may regulate bile acid metabolism in the liver. A synergistic interaction between an allele of this gene and the APOE E4 allele is associated with an elevated risk of Alzheimer's disease in human patients. [provided by RefSeq, Jul 2017]

MALRD1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0024554431).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.158 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MALRD1	NM_001142308.3 linkuse as main transcript	c.4538A>G	p.Asp1513Gly	missense_variant	27/40	ENST00000454679.7	NP_001135780.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MALRD1	ENST00000454679.7 linkuse as main transcript	c.4538A>G	p.Asp1513Gly	missense_variant	27/40	1	NM_001142308.3	ENSP00000412763	P1
MALRD1	ENST00000377266.7 linkuse as main transcript	c.2465A>G	p.Asp822Gly	missense_variant	13/25	5		ENSP00000366477

Frequencies

GnomAD3 genomes

AF:

0.115

AC:

17527

AN:

151960

Hom.:

1093

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0762

Gnomad AMI

AF:

0.134

Gnomad AMR

AF:

0.0966

Gnomad ASJ

AF:

0.0954

Gnomad EAS

AF:

0.143

Gnomad SAS

AF:

0.168

Gnomad FIN

AF:

0.0952

Gnomad MID

AF:

0.127

Gnomad NFE

AF:

0.141

Gnomad OTH

AF:

0.116

GnomAD3 exomes

AF:

0.122

AC:

18281

AN:

149300

Hom.:

1325

AF XY:

0.127

AC XY:

10242

AN XY:

80362

show subpopulations

Gnomad AFR exome

AF:

0.0777

Gnomad AMR exome

AF:

0.0650

Gnomad ASJ exome

AF:

0.0956

Gnomad EAS exome

AF:

0.146

Gnomad SAS exome

AF:

0.171

Gnomad FIN exome

AF:

0.0905

Gnomad NFE exome

AF:

0.143

Gnomad OTH exome

AF:

0.128

GnomAD4 exome

AF:

0.139

AC:

193839

AN:

1397862

Hom.:

14177

Cov.:

AF XY:

0.140

AC XY:

96418

AN XY:

689466

show subpopulations

Gnomad4 AFR exome

AF:

0.0741

Gnomad4 AMR exome

AF:

0.0681

Gnomad4 ASJ exome

AF:

0.0931

Gnomad4 EAS exome

AF:

0.111

Gnomad4 SAS exome

AF:

0.168

Gnomad4 FIN exome

AF:

0.0981

Gnomad4 NFE exome

AF:

0.145

Gnomad4 OTH exome

AF:

0.132

GnomAD4 genome

AF:

0.115

AC:

17530

AN:

152078

Hom.:

1091

Cov.:

AF XY:

0.114

AC XY:

8440

AN XY:

74324

show subpopulations

Gnomad4 AFR

AF:

0.0762

Gnomad4 AMR

AF:

0.0965

Gnomad4 ASJ

AF:

0.0954

Gnomad4 EAS

AF:

0.142

Gnomad4 SAS

AF:

0.167

Gnomad4 FIN

AF:

0.0952

Gnomad4 NFE

AF:

0.141

Gnomad4 OTH

AF:

0.117

Alfa

AF:

0.130

Hom.:

700

Bravo

AF:

0.113

TwinsUK

AF:

0.143

AC:

531

ALSPAC

AF:

0.146

AC:

562

ExAC

AF:

0.122

AC:

2478

Asia WGS

AF:

0.153

AC:

531

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.69

BayesDel_addAF

Benign

0.0093

BayesDel_noAF

Pathogenic

0.38

CADD

Uncertain

DANN

Uncertain

1.0

Eigen

Benign

0.086

Eigen_PC

Benign

0.089

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.84

T;T

MetaRNN

Benign

0.0025

T;T

MetaSVM

Benign

-0.97

MutationTaster

Benign

0.044

PROVEAN

Uncertain

-3.8

.;D

REVEL

Pathogenic

0.77

Sift

Benign

0.078

.;T

Sift4G

Uncertain

0.014

D;D

Vest4

0.23

ClinPred

0.020

GERP RS

3.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.065

gMVP

0.91

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over