Variant chr10-19203773-C-T 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.1997C>T(p.Ala666Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.14 in 1,549,776 control chromosomes in the GnomAD database, including 16,403 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 (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.13 ( 1378 hom., cov: 32)

Exomes 𝑓: 0.14 ( 15025 hom. )

Consequence

MALRD1
NM_001142308.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.76

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0017303824).

BP6

Variant 10-19203773-C-T is Benign according to our data. Variant chr10-19203773-C-T is described in ClinVar as [Benign]. Clinvar id is 769364.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.149 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.1997C>T	p.Ala666Val	missense_variant	15/40	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.1997C>T	p.Ala666Val	missense_variant	15/40	1	NM_001142308.3	ENSP00000412763	P1

Frequencies

GnomAD3 genomes

AF:

0.130

AC:

19739

AN:

151976

Hom.:

1375

Cov.:

show subpopulations

Gnomad AFR

AF:

0.118

Gnomad AMI

AF:

0.125

Gnomad AMR

AF:

0.131

Gnomad ASJ

AF:

0.173

Gnomad EAS

AF:

0.00116

Gnomad SAS

AF:

0.0507

Gnomad FIN

AF:

0.109

Gnomad MID

AF:

0.190

Gnomad NFE

AF:

0.152

Gnomad OTH

AF:

0.171

GnomAD4 exome

AF:

0.141

AC:

197280

AN:

1397682

Hom.:

15025

Cov.:

AF XY:

0.139

AC XY:

95560

AN XY:

689314

show subpopulations

Gnomad4 AFR exome

AF:

0.118

Gnomad4 AMR exome

AF:

0.0991

Gnomad4 ASJ exome

AF:

0.173

Gnomad4 EAS exome

AF:

0.000308

Gnomad4 SAS exome

AF:

0.0629

Gnomad4 FIN exome

AF:

0.109

Gnomad4 NFE exome

AF:

0.154

Gnomad4 OTH exome

AF:

0.136

GnomAD4 genome

AF:

0.130

AC:

19752

AN:

152094

Hom.:

1378

Cov.:

AF XY:

0.126

AC XY:

9336

AN XY:

74356

show subpopulations

Gnomad4 AFR

AF:

0.118

Gnomad4 AMR

AF:

0.131

Gnomad4 ASJ

AF:

0.173

Gnomad4 EAS

AF:

0.00116

Gnomad4 SAS

AF:

0.0506

Gnomad4 FIN

AF:

0.109

Gnomad4 NFE

AF:

0.152

Gnomad4 OTH

AF:

0.169

Alfa

AF:

0.150

Hom.:

2067

Bravo

AF:

0.132

TwinsUK

AF:

0.158

AC:

585

ALSPAC

AF:

0.147

AC:

565

Asia WGS

AF:

0.0360

AC:

126

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 20, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.62

CADD

Benign

DANN

Benign

0.64

FATHMM_MKL

Benign

0.52

LIST_S2

Benign

0.68

MetaRNN

Benign

0.0017

Sift4G

Benign

0.60

Vest4

0.071

MVP

0.12

GERP RS

3.4

Varity_R

0.057

gMVP

0.058

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