10-19615941-ATTT-ATTTT

Variant names:

• chr10-19615941-A-AT
• rs10580913
• NM_001142308.3:c.6137+29dupT

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.

The NM_001142308.3(MALRD1):​c.6137+29dupT variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000033 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0065 (0 hom.)
• Consequence: MALRD1 NM_001142308.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.149

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 Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MALRD1	NM_001142308.3	c.6137+29dupT		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+18_6137+19insT		intron_variant	Intron 36 of 39	1	NM_001142308.3	ENSP00000412763.3
MALRD1	ENST00000377266.7	c.4207+8039_4207+8040insT		intron_variant	Intron 22 of 24	5		ENSP00000366477.3
MALRD1	ENST00000377265.3	c.1187+18_1187+19insT		intron_variant	Intron 8 of 11	2		ENSP00000366476.3

Frequencies

GnomAD3 genomes AF: 0.0000334 AC: 5 AN: 149870 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0000490

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000978

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000297

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.0107 AC: 1142 AN: 106568 Hom.: 0 AF XY: 0.0106 AC XY: 610 AN XY: 57586

Gnomad AFR exome AF: 0.00758

Gnomad AMR exome AF: 0.0184

Gnomad ASJ exome AF: 0.0102

Gnomad EAS exome AF: 0.0127

Gnomad SAS exome AF: 0.0146

Gnomad FIN exome AF: 0.00466

Gnomad NFE exome AF: 0.00736

Gnomad OTH exome AF: 0.0117

GnomAD4 exome AF: 0.00649 AC: 8321 AN: 1281688 Hom.: 0 Cov.: 0 AF XY: 0.00669 AC XY: 4219 AN XY: 630684

Gnomad4 AFR exome AF: 0.00531

Gnomad4 AMR exome AF: 0.0132

Gnomad4 ASJ exome AF: 0.00825

Gnomad4 EAS exome AF: 0.00591

Gnomad4 SAS exome AF: 0.0137

Gnomad4 FIN exome AF: 0.00461

Gnomad4 NFE exome AF: 0.00586

Gnomad4 OTH exome AF: 0.00688

GnomAD4 genome AF: 0.0000333 AC: 5 AN: 149976 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 73170

Gnomad4 AFR AF: 0.0000489

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.0000978

Gnomad4 NFE AF: 0.0000297

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs10580913; hg19: chr10-19904870;