Genetic Variant AMMECR1:p.Glu287Asp (chrX-110200980-T-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_015365.3(AMMECR1):c.861A>T(p.Glu287Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000891 in 112,290 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. E287E) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0000089 ( 0 hom., 1 hem., cov: 23)

Consequence

AMMECR1
NM_015365.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.65

Publications

0 publications found

Variant links:

Genes affected

AMMECR1 (HGNC:467): (AMMECR nuclear protein 1) The exact function of this gene is not known, however, submicroscopic deletion of the X chromosome including this gene, COL4A5, and FACL4 genes, result in a contiguous gene deletion syndrome, the AMME complex (Alport syndrome, mental retardation, midface hypoplasia, and elliptocytosis). Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2010]

AMMECR1 Gene-Disease associations (from GenCC):

midface hypoplasia, hearing impairment, elliptocytosis, and nephrocalcinosis
Inheritance: XL Classification: STRONG, MODERATE Submitted by: Illumina, Labcorp Genetics (formerly Invitae)
Alport syndrome-intellectual disability-midface hypoplasia-elliptocytosis syndrome
Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet

AMMECR1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.11808616).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
AMMECR1	NM_015365.3 link	c.861A>T	p.Glu287Asp	missense_variant	Exon 5 of 6	ENST00000262844.10	NP_056180.1
AMMECR1	NM_001025580.2 link	c.750A>T	p.Glu250Asp	missense_variant	Exon 4 of 5		NP_001020751.1
AMMECR1	NM_001171689.2 link	c.492A>T	p.Glu164Asp	missense_variant	Exon 7 of 8		NP_001165160.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AMMECR1	ENST00000262844.10 link	c.861A>T	p.Glu287Asp	missense_variant	Exon 5 of 6	1	NM_015365.3	ENSP00000262844.5		Q9Y4X0-1

Frequencies

GnomAD3 genomes

AF:

0.00000891

AC:

AN:

112290

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000188

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000891

AC:

AN:

112290

Hom.:

Cov.:

AF XY:

0.0000290

AC XY:

AN XY:

34474

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30943

American (AMR)

AF:

0.00

AC:

AN:

10599

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2651

East Asian (EAS)

AF:

0.00

AC:

AN:

3588

South Asian (SAS)

AF:

0.00

AC:

AN:

2696

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6173

Middle Eastern (MID)

AF:

0.00

AC:

AN:

239

European-Non Finnish (NFE)

AF:

0.0000188

AC:

AN:

53206

Other (OTH)

AF:

0.00

AC:

AN:

1512

Alfa

AF:

0.000132

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.062

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.68

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.20

T;.;.

FATHMM_MKL

Uncertain

0.86

LIST_S2

Benign

0.80

T;T;T

M_CAP

Benign

0.0024

MetaRNN

Benign

0.12

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.13

N;.;.

PhyloP100

1.7

PrimateAI

Pathogenic

0.87

PROVEAN

Benign

-0.53

N;N;N

REVEL

Benign

0.069

Sift

Benign

0.64

T;T;T

Sift4G

Benign

0.66

T;T;T

Polyphen

0.024

B;B;.

Vest4

0.14

MutPred

0.56

Gain of helix (P = 0.132);.;.;

MVP

0.15

MPC

0.64

ClinPred

0.37

GERP RS

3.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.13

gMVP

0.71

Mutation Taster

=97/3

polymorphism

(source)

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

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X-110200980-T-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over