rs10827628

Variant names:

• chr10-19595335-G-A
• rs10827628
• NM_001142308.3:c.5822G>A

Your query was ambiguous. Multiple possible variants found:

• chr10-19595335-G-A
• chr10-19595335-G-C
• chr10-19595335-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001142308.3(MALRD1):​c.5822G>A​(p.Ser1941Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.515 in 1,550,002 control chromosomes in the GnomAD database, including 207,126 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/18 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.51 (19744 hom., cov: 30)
  • Exomes 𝑓: 0.52 (187382 hom.)
• Consequence: MALRD1 NM_001142308.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.64
• Publications: 11 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=9.011048E-5).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.524 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001142308.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MALRD1	NM_001142308.3	MANE Select	c.5822G>A	p.Ser1941Asn	missense	Exon 34 of 40	NP_001135780.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MALRD1	ENST00000454679.7	TSL:1 MANE Select	c.5822G>A	p.Ser1941Asn	missense	Exon 34 of 40	ENSP00000412763.3
	MALRD1	ENST00000377266.7	TSL:5	c.3959G>A	p.Ser1320Asn	missense	Exon 21 of 25	ENSP00000366477.3
	MALRD1	ENST00000377265.3	TSL:2	c.872G>A	p.Ser291Asn	missense	Exon 6 of 12	ENSP00000366476.3

Frequencies

GnomAD3 genomes AF: 0.509 AC: 77162 AN: 151644 Hom.: 19733 Cov.: 30

Gnomad AFR AF: 0.529

Gnomad AMI AF: 0.547

Gnomad AMR AF: 0.431

Gnomad ASJ AF: 0.449

Gnomad EAS AF: 0.368

Gnomad SAS AF: 0.384

Gnomad FIN AF: 0.560

Gnomad MID AF: 0.472

Gnomad NFE AF: 0.529

Gnomad OTH AF: 0.488

GnomAD2 exomes AF: 0.466 AC: 70277 AN: 150730 AF XY: 0.467

Gnomad AFR exome AF: 0.534

Gnomad AMR exome AF: 0.364

Gnomad ASJ exome AF: 0.438

Gnomad EAS exome AF: 0.365

Gnomad FIN exome AF: 0.563

Gnomad NFE exome AF: 0.525

Gnomad OTH exome AF: 0.481

GnomAD4 exome AF: 0.515 AC: 720707 AN: 1398238 Hom.: 187382 Cov.: 60 AF XY: 0.512 AC XY: 352838 AN XY: 689642

African (AFR) AF: 0.531 AC: 16769 AN: 31582

American (AMR) AF: 0.374 AC: 13340 AN: 35704

Ashkenazi Jewish (ASJ) AF: 0.443 AC: 11157 AN: 25178

East Asian (EAS) AF: 0.422 AC: 15083 AN: 35738

South Asian (SAS) AF: 0.397 AC: 31488 AN: 79226

European-Finnish (FIN) AF: 0.544 AC: 26269 AN: 48280

Middle Eastern (MID) AF: 0.440 AC: 2508 AN: 5702

European-Non Finnish (NFE) AF: 0.534 AC: 575547 AN: 1078752

Other (OTH) AF: 0.492 AC: 28546 AN: 58076

GnomAD4 genome AF: 0.509 AC: 77210 AN: 151764 Hom.: 19744 Cov.: 30 AF XY: 0.505 AC XY: 37458 AN XY: 74124

African (AFR) AF: 0.529 AC: 21896 AN: 41376

American (AMR) AF: 0.430 AC: 6560 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.449 AC: 1557 AN: 3468

East Asian (EAS) AF: 0.369 AC: 1889 AN: 5122

South Asian (SAS) AF: 0.386 AC: 1847 AN: 4788

European-Finnish (FIN) AF: 0.560 AC: 5905 AN: 10552

Middle Eastern (MID) AF: 0.473 AC: 139 AN: 294

European-Non Finnish (NFE) AF: 0.529 AC: 35895 AN: 67894

Other (OTH) AF: 0.486 AC: 1024 AN: 2108

Alfa AF: 0.516 Hom.: 63429

Bravo AF: 0.499

TwinsUK AF: 0.542 AC: 2011

ALSPAC AF: 0.535 AC: 2062

ExAC AF: 0.430 AC: 8957

Asia WGS AF: 0.415 AC: 1445 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.074
BayesDel_addAF	Benign	-0.54	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	6.6
DANN	Benign	0.97
Eigen	Benign	-0.38
Eigen_PC	Benign	-0.49
FATHMM_MKL	Benign	0.060	N
LIST_S2	Benign	0.25	T
MetaRNN	Benign	0.000090	T
MetaSVM	Benign	-0.97	T
PhyloP100		1.6
PROVEAN	Benign	-0.64	N
REVEL	Benign	0.043
Sift	Benign	0.053	T
Sift4G	Benign	0.27	T
Vest4		0.033
ClinPred		0.0042	T
GERP RS		3.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.056
gMVP		0.39
Mutation Taster		=97/3	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10827628; hg19: chr10-19884264; COSMIC: COSV63196343; COSMIC: COSV63196343;