Variant rs10827628 details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000454679.7(MALRD1):c.5822G>A(p.Ser1941Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.515 in 1,550,002 control chromosomes in the GnomAD database, including 207,126 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/16 in silico tools predict 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 0.51 ( 19744 hom., cov: 30)

Exomes 𝑓: 0.52 ( 187382 hom. )

Consequence

MALRD1
ENST00000454679.7 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.64

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=9.011048E-5).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.524 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.5822G>A	p.Ser1941Asn	missense_variant	34/40	ENST00000454679.7	NP_001135780.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
MALRD1	ENST00000454679.7 linkuse as main transcript	c.5822G>A	p.Ser1941Asn	missense_variant	34/40	1	NM_001142308.3	ENSP00000412763	P1
MALRD1	ENST00000377266.7 linkuse as main transcript	c.3959G>A	p.Ser1320Asn	missense_variant	21/25	5		ENSP00000366477
MALRD1	ENST00000377265.3 linkuse as main transcript	c.875G>A	p.Ser292Asn	missense_variant	6/12	2		ENSP00000366476

Frequencies

GnomAD3 genomes

AF:

0.509

AC:

77162

AN:

151644

Hom.:

19733

Cov.:

show subpopulations

Gnomad AFR

AF:

0.529

Gnomad AMI

AF:

0.547

Gnomad AMR

AF:

0.431

Gnomad ASJ

AF:

0.449

Gnomad EAS

AF:

0.368

Gnomad SAS

AF:

0.384

Gnomad FIN

AF:

0.560

Gnomad MID

AF:

0.472

Gnomad NFE

AF:

0.529

Gnomad OTH

AF:

0.488

GnomAD3 exomes

AF:

0.466

AC:

70277

AN:

150730

Hom.:

16942

AF XY:

0.467

AC XY:

37696

AN XY:

80802

show subpopulations

Gnomad AFR exome

AF:

0.534

Gnomad AMR exome

AF:

0.364

Gnomad ASJ exome

AF:

0.438

Gnomad EAS exome

AF:

0.365

Gnomad SAS exome

AF:

0.395

Gnomad FIN exome

AF:

0.563

Gnomad NFE exome

AF:

0.525

Gnomad OTH exome

AF:

0.481

GnomAD4 exome

AF:

0.515

AC:

720707

AN:

1398238

Hom.:

187382

Cov.:

AF XY:

0.512

AC XY:

352838

AN XY:

689642

show subpopulations

Gnomad4 AFR exome

AF:

0.531

Gnomad4 AMR exome

AF:

0.374

Gnomad4 ASJ exome

AF:

0.443

Gnomad4 EAS exome

AF:

0.422

Gnomad4 SAS exome

AF:

0.397

Gnomad4 FIN exome

AF:

0.544

Gnomad4 NFE exome

AF:

0.534

Gnomad4 OTH exome

AF:

0.492

GnomAD4 genome

AF:

0.509

AC:

77210

AN:

151764

Hom.:

19744

Cov.:

AF XY:

0.505

AC XY:

37458

AN XY:

74124

show subpopulations

Gnomad4 AFR

AF:

0.529

Gnomad4 AMR

AF:

0.430

Gnomad4 ASJ

AF:

0.449

Gnomad4 EAS

AF:

0.369

Gnomad4 SAS

AF:

0.386

Gnomad4 FIN

AF:

0.560

Gnomad4 NFE

AF:

0.529

Gnomad4 OTH

AF:

0.486

Alfa

AF:

0.517

Hom.:

40851

Bravo

AF:

0.499

TwinsUK

AF:

0.542

AC:

2011

ALSPAC

AF:

0.535

AC:

2062

ExAC

AF:

0.430

AC:

8957

Asia WGS

AF:

0.415

AC:

1445

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.074

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.41

CADD

Benign

6.6

DANN

Benign

0.97

Eigen

Benign

-0.38

Eigen_PC

Benign

-0.49

FATHMM_MKL

Benign

0.060

LIST_S2

Benign

0.25

T;T

MetaRNN

Benign

0.000090

T;T

MetaSVM

Benign

-0.97

MutationTaster

Benign

1.0

P;P

PROVEAN

Benign

-0.64

.;N

REVEL

Benign

0.043

Sift

Benign

0.053

.;T

Sift4G

Benign

0.27

T;T

Vest4

0.033

ClinPred

0.0042

GERP RS

3.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.056

gMVP

0.39

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