chr21-32298987-AACGCCTC-A

Position:

• chr21-32298987-AACGCCTC-A

Variant summary

Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PVS1_Strong PM2 PP5

The ENST00000303645.10(MRAP):​c.17_23delACGCCTC​(p.Asn6fs) 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 ENST00000303645.10 frameshift
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 4.32

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 (HGNC:):

ACMG classification

Verdict is Likely_pathogenic. Variant got 7 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.967 CDS is truncated, and there are 0 pathogenic variants in the truncated region.
• 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 id is 1843.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MRAP	NM_001379228.1	c.17_23delACGCCTC	p.Asn6fs	frameshift_variant	1/3	ENST00000303645.10	NP_001366157.1
MRAP	NM_178817.4	c.17_23delACGCCTC	p.Asn6fs	frameshift_variant	3/5		NP_848932.1
MRAP	NM_206898.2	c.17_23delACGCCTC	p.Asn6fs	frameshift_variant	3/5		NP_996781.1
MRAP	NM_001285394.2	c.-72+5856_-72+5862delACGCCTC		intron_variant			NP_001272323.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MRAP	ENST00000303645.10	c.17_23delACGCCTC	p.Asn6fs	frameshift_variant	1/3	1	NM_001379228.1	ENSP00000306697.5
MRAP	ENST00000399784.6	c.17_23delACGCCTC	p.Asn6fs	frameshift_variant	3/5	1		ENSP00000382684.2
MRAP	ENST00000339944.4	c.17_23delACGCCTC	p.Asn6fs	frameshift_variant	1/3	1		ENSP00000343661.4
MRAP	ENST00000497833.1	n.177+5856_177+5862delACGCCTC		intron_variant		1

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

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Glucocorticoid deficiency 2 Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Oct 01, 2006

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1569025178; hg19: chr21-33671298;