Variant rs12256835 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_001142308.3(MALRD1):c.5163T>G(p.His1721Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.207 in 1,548,422 control chromosomes in the GnomAD database, including 39,172 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/18 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 0.30 ( 8967 hom., cov: 32)

Exomes 𝑓: 0.20 ( 30205 hom. )

Consequence

MALRD1
NM_001142308.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.743

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:

MALRD1 (HGNC:):

MALRD1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.562 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.5163T>G	p.His1721Gln	missense_variant	31/40	ENST00000454679.7	NP_001135780.2	Q5VYJ5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
MALRD1	ENST00000454679.7 linkuse as main transcript	c.5163T>G	p.His1721Gln	missense_variant	31/40	1	NM_001142308.3	ENSP00000412763.3	Q5VYJ5
MALRD1	ENST00000377266.7 linkuse as main transcript	c.3300T>G	p.His1100Gln	missense_variant	18/25	5		ENSP00000366477.3	U5GXS0
MALRD1	ENST00000377265.3 linkuse as main transcript	c.213T>G	p.His71Gln	missense_variant	3/12	2		ENSP00000366476.3	H0Y3D6
MALRD1	ENST00000492202.1 linkuse as main transcript	n.291T>G		non_coding_transcript_exon_variant	4/5	4

Frequencies

GnomAD3 genomes

AF:

0.298

AC:

45285

AN:

151908

Hom.:

8950

Cov.:

show subpopulations

Gnomad AFR

AF:

0.568

Gnomad AMI

AF:

0.350

Gnomad AMR

AF:

0.212

Gnomad ASJ

AF:

0.339

Gnomad EAS

AF:

0.238

Gnomad SAS

AF:

0.208

Gnomad FIN

AF:

0.168

Gnomad MID

AF:

0.253

Gnomad NFE

AF:

0.182

Gnomad OTH

AF:

0.284

GnomAD3 exomes

AF:

0.224

AC:

33290

AN:

148786

Hom.:

4301

AF XY:

0.222

AC XY:

17765

AN XY:

80136

show subpopulations

Gnomad AFR exome

AF:

0.576

Gnomad AMR exome

AF:

0.208

Gnomad ASJ exome

AF:

0.341

Gnomad EAS exome

AF:

0.258

Gnomad SAS exome

AF:

0.208

Gnomad FIN exome

AF:

0.171

Gnomad NFE exome

AF:

0.186

Gnomad OTH exome

AF:

0.215

GnomAD4 exome

AF:

0.197

AC:

274844

AN:

1396396

Hom.:

30205

Cov.:

AF XY:

0.197

AC XY:

135346

AN XY:

688614

show subpopulations

Gnomad4 AFR exome

AF:

0.582

Gnomad4 AMR exome

AF:

0.211

Gnomad4 ASJ exome

AF:

0.347

Gnomad4 EAS exome

AF:

0.209

Gnomad4 SAS exome

AF:

0.206

Gnomad4 FIN exome

AF:

0.174

Gnomad4 NFE exome

AF:

0.180

Gnomad4 OTH exome

AF:

0.227

GnomAD4 genome

AF:

0.298

AC:

45345

AN:

152026

Hom.:

8967

Cov.:

AF XY:

0.292

AC XY:

21689

AN XY:

74346

show subpopulations

Gnomad4 AFR

AF:

0.568

Gnomad4 AMR

AF:

0.212

Gnomad4 ASJ

AF:

0.339

Gnomad4 EAS

AF:

0.238

Gnomad4 SAS

AF:

0.207

Gnomad4 FIN

AF:

0.168

Gnomad4 NFE

AF:

0.182

Gnomad4 OTH

AF:

0.281

Alfa

AF:

0.217

Hom.:

6411

Bravo

AF:

0.319

TwinsUK

AF:

0.187

AC:

695

ALSPAC

AF:

0.175

AC:

676

ExAC

AF:

0.220

AC:

4233

Asia WGS

AF:

0.216

AC:

750

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.076

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.20

CADD

Benign

DANN

Benign

0.60

Eigen

Benign

-0.76

Eigen_PC

Benign

-0.85

FATHMM_MKL

Benign

0.012

LIST_S2

Benign

0.053

T;T

MetaRNN

Benign

0.000090

T;T

MetaSVM

Benign

-0.93

PROVEAN

Benign

-0.11

.;N

REVEL

Uncertain

0.31

Sift

Benign

0.35

.;T

Sift4G

Benign

0.53

T;T

Vest4

0.017

ClinPred

0.0015

GERP RS

-1.6

Varity_R

0.025

gMVP

0.11

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.62

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.62

Position offset: 1

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