NM_001142308.3:c.6137+28_6137+29delTT

Variant names:

• chr10-19615941-ATT-A
• rs10580913
• NM_001142308.3:c.6137+28_6137+29delTT

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_001142308.3(MALRD1):​c.6137+28_6137+29delTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.521 in 1,456,938 control chromosomes in the GnomAD database, including 194,852 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.45 (15691 hom., cov: 0)
  • Exomes 𝑓: 0.53 (179161 hom.)
• Consequence: MALRD1 NM_001142308.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.565

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

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.525 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MALRD1	NM_001142308.3	c.6137+28_6137+29delTT		intron_variant	Intron 36 of 39	ENST00000454679.7	NP_001135780.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MALRD1	ENST00000454679.7	c.6137+19_6137+20delTT		intron_variant	Intron 36 of 39	1	NM_001142308.3	ENSP00000412763.3
MALRD1	ENST00000377266.7	c.4207+8040_4207+8041delTT		intron_variant	Intron 22 of 24	5		ENSP00000366477.3
MALRD1	ENST00000377265.3	c.1187+19_1187+20delTT		intron_variant	Intron 8 of 11	2		ENSP00000366476.3

Frequencies

GnomAD3 genomes AF: 0.453 AC: 67819 AN: 149792 Hom.: 15689 Cov.: 0

Gnomad AFR AF: 0.327

Gnomad AMI AF: 0.545

Gnomad AMR AF: 0.410

Gnomad ASJ AF: 0.431

Gnomad EAS AF: 0.428

Gnomad SAS AF: 0.346

Gnomad FIN AF: 0.570

Gnomad MID AF: 0.445

Gnomad NFE AF: 0.530

Gnomad OTH AF: 0.447

GnomAD3 exomes AF: 0.547 AC: 58283 AN: 106568 Hom.: 13691 AF XY: 0.552 AC XY: 31760 AN XY: 57586

Gnomad AFR exome AF: 0.381

Gnomad AMR exome AF: 0.479

Gnomad ASJ exome AF: 0.521

Gnomad EAS exome AF: 0.529

Gnomad SAS exome AF: 0.482

Gnomad FIN exome AF: 0.610

Gnomad NFE exome AF: 0.610

Gnomad OTH exome AF: 0.575

GnomAD4 exome AF: 0.529 AC: 691743 AN: 1307040 Hom.: 179161 AF XY: 0.526 AC XY: 339095 AN XY: 644260

Gnomad4 AFR exome AF: 0.334

Gnomad4 AMR exome AF: 0.392

Gnomad4 ASJ exome AF: 0.455

Gnomad4 EAS exome AF: 0.505

Gnomad4 SAS exome AF: 0.391

Gnomad4 FIN exome AF: 0.560

Gnomad4 NFE exome AF: 0.552

Gnomad4 OTH exome AF: 0.502

GnomAD4 genome AF: 0.453 AC: 67847 AN: 149898 Hom.: 15691 Cov.: 0 AF XY: 0.449 AC XY: 32833 AN XY: 73126

Gnomad4 AFR AF: 0.327

Gnomad4 AMR AF: 0.410

Gnomad4 ASJ AF: 0.431

Gnomad4 EAS AF: 0.429

Gnomad4 SAS AF: 0.348

Gnomad4 FIN AF: 0.570

Gnomad4 NFE AF: 0.530

Gnomad4 OTH AF: 0.445

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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

Other links and lift over

dbSNP: rs10580913; hg19: chr10-19904870;