Variant 10-19491622-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_ModerateBS2

The NM_001142308.3(MALRD1):c.5135A>G(p.Asp1712Gly) variant causes a missense change. The variant allele was found at a frequency of 0.0125 in 1,549,642 control chromosomes in the GnomAD database, including 178 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.011 ( 26 hom., cov: 33)

Exomes 𝑓: 0.013 ( 152 hom. )

Consequence

MALRD1
NM_001142308.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 6.89

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 Likely_benign. Variant got -6 ACMG points.

BP6

Variant 10-19491622-A-G is Benign according to our data. Variant chr10-19491622-A-G is described in ClinVar as [Benign]. Clinvar id is 770763.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd at 26 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MALRD1	NM_001142308.3 linkuse as main transcript	c.5135A>G	p.Asp1712Gly	missense_variant	30/40	ENST00000454679.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
MALRD1	ENST00000454679.7 linkuse as main transcript	c.5135A>G	p.Asp1712Gly	missense_variant	30/40	1	NM_001142308.3	P1
MALRD1	ENST00000377266.7 linkuse as main transcript	c.3272A>G	p.Asp1091Gly	missense_variant	17/25	5
MALRD1	ENST00000377265.3 linkuse as main transcript	c.188A>G	p.Asp63Gly	missense_variant	2/12	2
MALRD1	ENST00000492202.1 linkuse as main transcript	n.185A>G		non_coding_transcript_exon_variant	2/5	4

Frequencies

GnomAD3 genomes

AF:

0.0115

AC:

1748

AN:

152136

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00217

Gnomad AMI

AF:

0.0110

Gnomad AMR

AF:

0.00812

Gnomad ASJ

AF:

0.0138

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00290

Gnomad FIN

AF:

0.0514

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0132

Gnomad OTH

AF:

0.00621

GnomAD3 exomes

AF:

0.0111

AC:

1662

AN:

149238

Hom.:

AF XY:

0.0106

AC XY:

850

AN XY:

80378

show subpopulations

Gnomad AFR exome

AF:

0.00160

Gnomad AMR exome

AF:

0.00313

Gnomad ASJ exome

AF:

0.0150

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00124

Gnomad FIN exome

AF:

0.0431

Gnomad NFE exome

AF:

0.0123

Gnomad OTH exome

AF:

0.00693

GnomAD4 exome

AF:

0.0126

AC:

17646

AN:

1397390

Hom.:

152

Cov.:

AF XY:

0.0123

AC XY:

8460

AN XY:

689268

show subpopulations

Gnomad4 AFR exome

AF:

0.00149

Gnomad4 AMR exome

AF:

0.00294

Gnomad4 ASJ exome

AF:

0.0139

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00126

Gnomad4 FIN exome

AF:

0.0409

Gnomad4 NFE exome

AF:

0.0134

Gnomad4 OTH exome

AF:

0.0102

GnomAD4 genome

AF:

0.0115

AC:

1748

AN:

152252

Hom.:

Cov.:

AF XY:

0.0126

AC XY:

937

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.00217

Gnomad4 AMR

AF:

0.00811

Gnomad4 ASJ

AF:

0.0138

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00290

Gnomad4 FIN

AF:

0.0514

Gnomad4 NFE

AF:

0.0132

Gnomad4 OTH

AF:

0.00614

Alfa

AF:

0.0112

Hom.:

Bravo

AF:

0.00806

TwinsUK

AF:

0.0119

AC:

ALSPAC

AF:

0.0174

AC:

ExAC

AF:

0.00930

AC:

191

Asia WGS

AF:

0.00115

AC:

AN:

3478

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

Invitae

Jun 08, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.47

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Uncertain

0.030

Cadd

Pathogenic

Dann

Uncertain

0.99

Eigen

Benign

0.063

Eigen_PC

Benign

0.036

FATHMM_MKL

Uncertain

0.83

LIST_S2

Uncertain

0.88

D;T

MetaRNN

Benign

0.0047

T;T

MetaSVM

Benign

-0.87

MutationTaster

Benign

1.0

N;N

REVEL

Uncertain

0.58

Sift4G

Pathogenic

0.0

D;T

Vest4

0.86

ClinPred

0.046

GERP RS

5.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.19

gMVP

0.85

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.69

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.69

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over