21-32298987-AACGCCTC-A

Variant names:

• chr21-32298987-AACGCCTC-A
• rs1569025178
• NM_001379228.1:c.17_23delACGCCTC

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP5

The NM_001379228.1(MRAP):​c.17_23delACGCCTC​(p.Asn6MetfsTer24) variant causes a frameshift change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 33)
• Consequence: MRAP NM_001379228.1 frameshift
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 4.32
• Publications: 0 publications found

Genes affected

MRAP (HGNC:1304): (melanocortin 2 receptor accessory protein) This gene encodes a melanocortin receptor-interacting protein. The encoded protein regulates trafficking and function of the melanocortin 2 receptor in the adrenal gland. The encoded protein can also modulate signaling of other melanocortin receptors. Mutations in this gene have been associated with familial glucocorticoid deficiency type 2. Alternatively spliced transcript variants have been described. [provided by RefSeq, Dec 2009]

MRAP-AS1 (HGNC:40108): (MRAP antisense RNA 1)

LOC124905009 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 21-32298987-AACGCCTC-A is Pathogenic according to our data. Variant chr21-32298987-AACGCCTC-A is described in ClinVar as Pathogenic. ClinVar VariationId is 1843.Status of the report is no_assertion_criteria_provided, 0 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001379228.1. 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
	MRAP	NM_001379228.1	MANE Select	c.17_23delACGCCTC	p.Asn6MetfsTer24	frameshift	Exon 1 of 3	NP_001366157.1	Q8TCY5-4
	MRAP	NM_178817.4		c.17_23delACGCCTC	p.Asn6MetfsTer24	frameshift	Exon 3 of 5	NP_848932.1	Q8TCY5-4
	MRAP	NM_206898.2		c.17_23delACGCCTC	p.Asn6MetfsTer24	frameshift	Exon 3 of 5	NP_996781.1	Q8TCY5-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MRAP	ENST00000303645.10	TSL:1 MANE Select	c.17_23delACGCCTC	p.Asn6MetfsTer24	frameshift	Exon 1 of 3	ENSP00000306697.5	Q8TCY5-4
	MRAP	ENST00000399784.6	TSL:1	c.17_23delACGCCTC	p.Asn6MetfsTer24	frameshift	Exon 3 of 5	ENSP00000382684.2	Q8TCY5-4
	MRAP	ENST00000339944.4	TSL:1	c.17_23delACGCCTC	p.Asn6MetfsTer24	frameshift	Exon 1 of 3	ENSP00000343661.4	Q8TCY5-2

Frequencies

GnomAD3 genomes Cov.: 33

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

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Pathogenic

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
1	-	-	Glucocorticoid deficiency 2 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		4.3
Mutation Taster		=30/170	disease causing (ClinVar)

Splicing

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

Other links and lift over

dbSNP: rs1569025178; hg19: chr21-33671298;