dbSNP rs1249311661: MRAP:p.Asp27Glu (chr21-32299052-C-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001379228.1(MRAP):c.81C>A(p.Asp27Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,698 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. D27D) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

MRAP
NM_001379228.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.166

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 Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MRAP	NM_001379228.1 link	c.81C>A	p.Asp27Glu	missense_variant	Exon 1 of 3	ENST00000303645.10	NP_001366157.1
MRAP	NM_178817.4 link	c.81C>A	p.Asp27Glu	missense_variant	Exon 3 of 5		NP_848932.1	Q8TCY5-4
MRAP	NM_206898.2 link	c.81C>A	p.Asp27Glu	missense_variant	Exon 3 of 5		NP_996781.1	Q8TCY5-2
MRAP	NM_001285394.2 link	c.-72+5920C>A		intron_variant	Intron 2 of 3		NP_001272323.1	Q8TCY5-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
MRAP	ENST00000303645.10 link	c.81C>A	p.Asp27Glu	missense_variant	Exon 1 of 3	1	NM_001379228.1	ENSP00000306697.5	Q8TCY5-4
MRAP	ENST00000399784.6 link	c.81C>A	p.Asp27Glu	missense_variant	Exon 3 of 5	1		ENSP00000382684.2	Q8TCY5-4
MRAP	ENST00000339944.4 link	c.81C>A	p.Asp27Glu	missense_variant	Exon 1 of 3	1		ENSP00000343661.4	Q8TCY5-2
MRAP	ENST00000497833.1 link	n.177+5920C>A		intron_variant	Intron 2 of 3	1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461698

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727148

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.73

BayesDel_addAF

Uncertain

0.15

BayesDel_noAF

Uncertain

-0.030

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.50

D;D;.

Eigen

Benign

-0.27

Eigen_PC

Benign

-0.40

FATHMM_MKL

Benign

0.46

LIST_S2

Benign

0.74

.;T;T

M_CAP

Uncertain

0.15

MetaRNN

Uncertain

0.66

D;D;D

MetaSVM

Uncertain

0.017

MutationAssessor

Uncertain

2.2

M;M;M

PrimateAI

Uncertain

0.54

PROVEAN

Uncertain

-2.6

D;D;D

REVEL

Uncertain

0.54

Sift

Uncertain

0.0050

D;D;D

Sift4G

Pathogenic

0.0

D;D;D

Polyphen

1.0

D;D;D

Vest4

0.70

MutPred

0.34

Loss of loop (P = 0.0374);Loss of loop (P = 0.0374);Loss of loop (P = 0.0374);

MVP

0.85

MPC

0.40

ClinPred

0.99

GERP RS

-5.3

Varity_R

0.23

gMVP

0.33

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over