21-32299080-A-AT

Position:

• chr21-32299080-A-AT

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP5

The ENST00000303645.10(MRAP):​c.106+3_106+4insT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 1/1 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 33)
• Consequence: MRAP ENST00000303645.10 splice_region, intron
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 3.58

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 Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 21-32299080-A-AT is Pathogenic according to our data. Variant chr21-32299080-A-AT is described in ClinVar as [Pathogenic]. Clinvar id is 1840.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.106+3_106+4insT		splice_region_variant, intron_variant		ENST00000303645.10	NP_001366157.1
MRAP	NM_178817.4	c.106+3_106+4insT		splice_region_variant, intron_variant			NP_848932.1
MRAP	NM_001285394.2	c.-72+5948_-72+5949insT		intron_variant			NP_001272323.1
MRAP	NM_206898.2	c.106+3_106+4insT		splice_region_variant, intron_variant			NP_996781.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MRAP	ENST00000303645.10	c.106+3_106+4insT		splice_region_variant, intron_variant		1	NM_001379228.1	ENSP00000306697.5
MRAP	ENST00000399784.6	c.106+3_106+4insT		splice_region_variant, intron_variant		1		ENSP00000382684.2
MRAP	ENST00000339944.4	c.106+3_106+4insT		splice_region_variant, intron_variant		1		ENSP00000343661.4
MRAP	ENST00000497833.1	n.177+5948_177+5949insT		intron_variant		1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 29

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

Feb 01, 2005

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.93		Details are displayed if max score is > 0.2
DS_DL_spliceai		0.93		Position offset: -3

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr21-33671391;