Variant chr10-19136602-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001142308.3(MALRD1):c.1232A>G(p.Gln411Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.199 in 1,230,686 control chromosomes in the GnomAD database, including 25,877 homozygotes. In-silico tool predicts a benign outcome for this variant. 8/11 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.17 ( 2803 hom., cov: 32)

Exomes 𝑓: 0.20 ( 23074 hom. )

Consequence

MALRD1
NM_001142308.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.42

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0015641153).

BP6

Variant 10-19136602-A-G is Benign according to our data. Variant chr10-19136602-A-G is described in ClinVar as [Benign]. Clinvar id is 769362.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.246 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.1232A>G	p.Gln411Arg	missense_variant	10/40	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.1232A>G	p.Gln411Arg	missense_variant	10/40	1	NM_001142308.3	ENSP00000412763	P1

Frequencies

GnomAD3 genomes

AF:

0.168

AC:

25579

AN:

152034

Hom.:

2800

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0400

Gnomad AMI

AF:

0.0559

Gnomad AMR

AF:

0.252

Gnomad ASJ

AF:

0.224

Gnomad EAS

AF:

0.146

Gnomad SAS

AF:

0.117

Gnomad FIN

AF:

0.270

Gnomad MID

AF:

0.171

Gnomad NFE

AF:

0.216

Gnomad OTH

AF:

0.161

GnomAD4 exome

AF:

0.203

AC:

219148

AN:

1078534

Hom.:

23074

Cov.:

AF XY:

0.204

AC XY:

103727

AN XY:

509104

show subpopulations

Gnomad4 AFR exome

AF:

0.0295

Gnomad4 AMR exome

AF:

0.292

Gnomad4 ASJ exome

AF:

0.226

Gnomad4 EAS exome

AF:

0.163

Gnomad4 SAS exome

AF:

0.122

Gnomad4 FIN exome

AF:

0.256

Gnomad4 NFE exome

AF:

0.209

Gnomad4 OTH exome

AF:

0.189

GnomAD4 genome

AF:

0.168

AC:

25583

AN:

152152

Hom.:

2803

Cov.:

AF XY:

0.171

AC XY:

12757

AN XY:

74386

show subpopulations

Gnomad4 AFR

AF:

0.0398

Gnomad4 AMR

AF:

0.253

Gnomad4 ASJ

AF:

0.224

Gnomad4 EAS

AF:

0.145

Gnomad4 SAS

AF:

0.118

Gnomad4 FIN

AF:

0.270

Gnomad4 NFE

AF:

0.216

Gnomad4 OTH

AF:

0.159

Alfa

AF:

0.199

Hom.:

902

Bravo

AF:

0.162

TwinsUK

AF:

0.211

AC:

781

ALSPAC

AF:

0.207

AC:

797

Asia WGS

AF:

0.142

AC:

493

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jun 10, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.089

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.51

CADD

Benign

DANN

Benign

0.86

FATHMM_MKL

Benign

0.042

LIST_S2

Benign

0.37

MetaRNN

Benign

0.0016

Sift4G

Uncertain

0.037

Vest4

0.077

MVP

0.15

GERP RS

2.7

Varity_R

0.034

gMVP

0.036

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