10-19595335-GC-AT

Variant names:

• chr10-19595335-GC-AT
• NM_001142308.3:c.5822_5823delGCinsAT
• MALRD1 p.Ser1941Asn

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001142308.3(MALRD1):​c.5822_5823delGCinsAT​(p.Ser1941Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. The variant is present in control chromosomes in GnomAd MNV project. The variant allele was found at a frequency of 0.0000319 in 1 alleles, including 0 homozygotes. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: GnomAD MNV: 𝑓 0.000032 Genomes: not found (cov: 30)
• Consequence: MALRD1 NM_001142308.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.64
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MALRD1	NM_001142308.3	MANE Select	c.5822_5823delGCinsAT	p.Ser1941Asn	missense	N/A	NP_001135780.2	Q5VYJ5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MALRD1	ENST00000454679.7	TSL:1 MANE Select	c.5822_5823delGCinsAT	p.Ser1941Asn	missense	N/A	ENSP00000412763.3	Q5VYJ5
	MALRD1	ENST00000377266.7	TSL:5	c.3959_3960delGCinsAT	p.Ser1320Asn	missense	N/A	ENSP00000366477.3	U5GXS0
	MALRD1	ENST00000377265.3	TSL:2	c.872_873delGCinsAT	p.Ser291Asn	missense	N/A	ENSP00000366476.3	H0Y3D6

Frequencies

GnomAD3 genomes Cov.: 30

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 30

GnomAD MNV AF: 0.0000319 AC: 1 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.6

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr10-19884264;