dbSNP rs57243552: MALRD1:p.Gln205Gln (chr10-19103996-A-G) – ACMG Classification: Benign (-21 pts)

Variant summary

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

The NM_001142308.3(MALRD1):c.615A>G(p.Gln205Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0512 in 1,233,286 control chromosomes in the GnomAD database, including 2,970 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.064 ( 479 hom., cov: 32)

Exomes 𝑓: 0.049 ( 2491 hom. )

Consequence

MALRD1
NM_001142308.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.221

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=-0.58).

BP6

Variant 10-19103996-A-G is Benign according to our data. Variant chr10-19103996-A-G is described in ClinVar as [Benign]. Clinvar id is 771739.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.221 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.263 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MALRD1	NM_001142308.3 link	c.615A>G	p.Gln205Gln	synonymous_variant	Exon 5 of 40	ENST00000454679.7	NP_001135780.2	Q5VYJ5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MALRD1	ENST00000454679.7 link	c.615A>G	p.Gln205Gln	synonymous_variant	Exon 5 of 40	1	NM_001142308.3	ENSP00000412763.3		Q5VYJ5

Frequencies

GnomAD3 genomes

AF:

0.0640

AC:

9723

AN:

152030

Hom.:

481

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0889

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.0529

Gnomad ASJ

AF:

0.0196

Gnomad EAS

AF:

0.274

Gnomad SAS

AF:

0.0792

Gnomad FIN

AF:

0.0503

Gnomad MID

AF:

0.0728

Gnomad NFE

AF:

0.0395

Gnomad OTH

AF:

0.0590

GnomAD4 exome

AF:

0.0494

AC:

53405

AN:

1081138

Hom.:

2491

Cov.:

AF XY:

0.0491

AC XY:

25037

AN XY:

510422

show subpopulations

Gnomad4 AFR exome

AF:

0.0878

Gnomad4 AMR exome

AF:

0.0635

Gnomad4 ASJ exome

AF:

0.0222

Gnomad4 EAS exome

AF:

0.305

Gnomad4 SAS exome

AF:

0.0673

Gnomad4 FIN exome

AF:

0.0426

Gnomad4 NFE exome

AF:

0.0406

Gnomad4 OTH exome

AF:

0.0612

GnomAD4 genome

AF:

0.0640

AC:

9742

AN:

152148

Hom.:

479

Cov.:

AF XY:

0.0661

AC XY:

4920

AN XY:

74384

show subpopulations

Gnomad4 AFR

AF:

0.0890

Gnomad4 AMR

AF:

0.0530

Gnomad4 ASJ

AF:

0.0196

Gnomad4 EAS

AF:

0.275

Gnomad4 SAS

AF:

0.0801

Gnomad4 FIN

AF:

0.0503

Gnomad4 NFE

AF:

0.0395

Gnomad4 OTH

AF:

0.0583

Alfa

AF:

0.0454

Hom.:

Bravo

AF:

0.0658

Asia WGS

AF:

0.162

AC:

563

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

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 06, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.58

CADD

Benign

2.7

DANN

Benign

0.69

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