Variant 10-19128252-T-C 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.975T>C(p.Gly325=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.174 in 1,232,914 control chromosomes in the GnomAD database, including 19,948 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.13 ( 1676 hom., cov: 33)

Exomes 𝑓: 0.18 ( 18272 hom. )

Consequence

MALRD1
NM_001142308.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.165

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=-0.86).

BP6

Variant 10-19128252-T-C is Benign according to our data. Variant chr10-19128252-T-C is described in ClinVar as [Benign]. Clinvar id is 769770.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.165 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.184 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.975T>C	p.Gly325=	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.975T>C	p.Gly325=	synonymous_variant	8/40	1	NM_001142308.3	ENSP00000412763	P1

Frequencies

GnomAD3 genomes

AF:

0.133

AC:

20285

AN:

152126

Hom.:

1673

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0416

Gnomad AMI

AF:

0.213

Gnomad AMR

AF:

0.139

Gnomad ASJ

AF:

0.160

Gnomad EAS

AF:

0.0998

Gnomad SAS

AF:

0.160

Gnomad FIN

AF:

0.126

Gnomad MID

AF:

0.180

Gnomad NFE

AF:

0.186

Gnomad OTH

AF:

0.160

GnomAD4 exome

AF:

0.180

AC:

194624

AN:

1080670

Hom.:

18272

Cov.:

AF XY:

0.181

AC XY:

92103

AN XY:

510194

show subpopulations

Gnomad4 AFR exome

AF:

0.0381

Gnomad4 AMR exome

AF:

0.139

Gnomad4 ASJ exome

AF:

0.158

Gnomad4 EAS exome

AF:

0.115

Gnomad4 SAS exome

AF:

0.165

Gnomad4 FIN exome

AF:

0.135

Gnomad4 NFE exome

AF:

0.188

Gnomad4 OTH exome

AF:

0.166

GnomAD4 genome

AF:

0.133

AC:

20285

AN:

152244

Hom.:

1676

Cov.:

AF XY:

0.131

AC XY:

9720

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.0415

Gnomad4 AMR

AF:

0.139

Gnomad4 ASJ

AF:

0.160

Gnomad4 EAS

AF:

0.100

Gnomad4 SAS

AF:

0.160

Gnomad4 FIN

AF:

0.126

Gnomad4 NFE

AF:

0.186

Gnomad4 OTH

AF:

0.157

Alfa

AF:

0.178

Hom.:

3751

Bravo

AF:

0.129

Asia WGS

AF:

0.121

AC:

420

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	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Apr 26, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.96

DANN

Benign

0.43

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