Variant 21-32298972-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate

The NM_001379228.1(MRAP):c.1A>G(p.Met1?) variant causes a start lost change. The variant allele was found at a frequency of 0.00000411 in 1,459,782 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

MRAP
NM_001379228.1 start_lost

Scores

Clinical Significance

Pathogenic criteria provided, single submitter P:1

Conservation

PhyloP100: 5.13

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Pathogenic. Variant got 12 ACMG points.

PVS1

Start lost variant, no new inframe start found.

PM2

Very rare variant in population databases, with high coverage;

PP5

Variant 21-32298972-A-G is Pathogenic according to our data. Variant chr21-32298972-A-G is described in ClinVar as [Pathogenic]. Clinvar id is 444067.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
MRAP	NM_001379228.1 linkuse as main transcript	c.1A>G	p.Met1?	start_lost	1/3	ENST00000303645.10	NP_001366157.1
MRAP	NM_178817.4 linkuse as main transcript	c.1A>G	p.Met1?	start_lost	3/5		NP_848932.1
MRAP	NM_206898.2 linkuse as main transcript	c.1A>G	p.Met1?	start_lost	3/5		NP_996781.1
MRAP	NM_001285394.2 linkuse as main transcript	c.-72+5840A>G		intron_variant			NP_001272323.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MRAP	ENST00000303645.10 linkuse as main transcript	c.1A>G	p.Met1?	start_lost	1/3	1	NM_001379228.1	ENSP00000306697	P1	Q8TCY5-4
MRAP	ENST00000399784.6 linkuse as main transcript	c.1A>G	p.Met1?	start_lost	3/5	1		ENSP00000382684	P1	Q8TCY5-4
MRAP	ENST00000339944.4 linkuse as main transcript	c.1A>G	p.Met1?	start_lost	1/3	1		ENSP00000343661		Q8TCY5-2
MRAP	ENST00000497833.1 linkuse as main transcript	n.177+5840A>G		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000411

AC:

AN:

1459782

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

726296

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000540

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Glucocorticoid deficiency 1

Pathogenic:1

Pathogenic, criteria provided, single submitter

clinical testing

Institute of Human Genetics Munich, Klinikum Rechts Der Isar, TU München

Sep 30, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Pathogenic

0.42

BayesDel_noAF

Pathogenic

0.37

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.31

T;T;.

Eigen

Uncertain

0.34

Eigen_PC

Uncertain

0.34

FATHMM_MKL

Uncertain

0.82

LIST_S2

Uncertain

0.90

.;D;D

M_CAP

Pathogenic

0.68

MetaRNN

Pathogenic

0.99

D;D;D

MetaSVM

Uncertain

0.37

MutationTaster

Benign

1.0

D;D;D

PROVEAN

Benign

-2.3

N;N;N

REVEL

Pathogenic

0.72

Sift

Pathogenic

0.0

D;D;D

Sift4G

Pathogenic

0.0

D;D;D

Polyphen

0.96

D;D;P

Vest4

0.89

MutPred

1.0

Loss of glycosylation at T5 (P = 0.2209);Loss of glycosylation at T5 (P = 0.2209);Loss of glycosylation at T5 (P = 0.2209);

MVP

0.95

ClinPred

0.99

GERP RS

5.1

Varity_R

0.93

gMVP

0.28

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over