Variant 10-19165736-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001142308.3(MALRD1):c.1756T>G(p.Phe586Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00243 in 1,231,686 control chromosomes in the GnomAD database, including 42 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 0.0025 ( 8 hom., cov: 31)

Exomes 𝑓: 0.0024 ( 34 hom. )

Consequence

MALRD1
NM_001142308.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.944

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 -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0045844316).

BP6

Variant 10-19165736-T-G is Benign according to our data. Variant chr10-19165736-T-G is described in ClinVar as [Benign]. Clinvar id is 2640342.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MALRD1	NM_001142308.3 linkuse as main transcript	c.1756T>G	p.Phe586Val	missense_variant	13/40	ENST00000454679.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MALRD1	ENST00000454679.7 linkuse as main transcript	c.1756T>G	p.Phe586Val	missense_variant	13/40	1	NM_001142308.3	P1

Frequencies

GnomAD3 genomes

AF:

0.00249

AC:

379

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000362

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000327

Gnomad ASJ

AF:

0.0646

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.000753

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00172

Gnomad OTH

AF:

0.00382

GnomAD4 exome

AF:

0.00242

AC:

2608

AN:

1079372

Hom.:

Cov.:

AF XY:

0.00250

AC XY:

1272

AN XY:

509498

show subpopulations

Gnomad4 AFR exome

AF:

0.0000435

Gnomad4 AMR exome

AF:

0.000950

Gnomad4 ASJ exome

AF:

0.0624

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00108

Gnomad4 FIN exome

AF:

0.000758

Gnomad4 NFE exome

AF:

0.00153

Gnomad4 OTH exome

AF:

0.00570

GnomAD4 genome

AF:

0.00249

AC:

379

AN:

152314

Hom.:

Cov.:

AF XY:

0.00227

AC XY:

169

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.000361

Gnomad4 AMR

AF:

0.000327

Gnomad4 ASJ

AF:

0.0646

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.000753

Gnomad4 NFE

AF:

0.00172

Gnomad4 OTH

AF:

0.00378

Alfa

AF:

0.00388

Hom.:

Bravo

AF:

0.00270

TwinsUK

AF:

0.00243

AC:

ALSPAC

AF:

0.00156

AC:

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jun 01, 2023

MALRD1: BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.075

BayesDel_addAF

Benign

-0.76

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.11

DANN

Benign

0.36

FATHMM_MKL

Benign

0.037

LIST_S2

Benign

0.31

MetaRNN

Benign

0.0046

Sift4G

Benign

0.21

Vest4

0.23

MVP

0.19

GERP RS

-5.3

Varity_R

0.084

gMVP

0.065

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