Variant 10-19128279-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001142308.3(MALRD1):c.1002G>A(p.Arg334=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0701 in 1,233,156 control chromosomes in the GnomAD database, including 3,356 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.084 ( 657 hom., cov: 33)

Exomes 𝑓: 0.068 ( 2699 hom. )

Consequence

MALRD1
NM_001142308.3 synonymous

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.892

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.75).

BP6

Variant 10-19128279-G-A is Benign according to our data. Variant chr10-19128279-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 768351.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.892 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.123 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.1002G>A	p.Arg334=	synonymous_variant	8/40	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.1002G>A	p.Arg334=	synonymous_variant	8/40	1	NM_001142308.3	ENSP00000412763	P1

Frequencies

GnomAD3 genomes

AF:

0.0840

AC:

12774

AN:

152044

Hom.:

657

Cov.:

show subpopulations

Gnomad AFR

AF:

0.125

Gnomad AMI

AF:

0.0275

Gnomad AMR

AF:

0.0746

Gnomad ASJ

AF:

0.0734

Gnomad EAS

AF:

0.00135

Gnomad SAS

AF:

0.0190

Gnomad FIN

AF:

0.103

Gnomad MID

AF:

0.120

Gnomad NFE

AF:

0.0700

Gnomad OTH

AF:

0.0846

GnomAD4 exome

AF:

0.0681

AC:

73627

AN:

1080994

Hom.:

2699

Cov.:

AF XY:

0.0676

AC XY:

34484

AN XY:

510360

show subpopulations

Gnomad4 AFR exome

AF:

0.129

Gnomad4 AMR exome

AF:

0.0685

Gnomad4 ASJ exome

AF:

0.0811

Gnomad4 EAS exome

AF:

0.000604

Gnomad4 SAS exome

AF:

0.0193

Gnomad4 FIN exome

AF:

0.0903

Gnomad4 NFE exome

AF:

0.0688

Gnomad4 OTH exome

AF:

0.0668

GnomAD4 genome

AF:

0.0840

AC:

12785

AN:

152162

Hom.:

657

Cov.:

AF XY:

0.0844

AC XY:

6278

AN XY:

74388

show subpopulations

Gnomad4 AFR

AF:

0.126

Gnomad4 AMR

AF:

0.0745

Gnomad4 ASJ

AF:

0.0734

Gnomad4 EAS

AF:

0.00135

Gnomad4 SAS

AF:

0.0182

Gnomad4 FIN

AF:

0.103

Gnomad4 NFE

AF:

0.0700

Gnomad4 OTH

AF:

0.0833

Alfa

AF:

0.0801

Hom.:

111

Bravo

AF:

0.0842

Asia WGS

AF:

0.0190

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jun 19, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

3.9

DANN

Benign

0.63

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over