X-110198556-A-C

Variant names:

Variant summary

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

The NM_015365.3(AMMECR1):c.966T>G(p.Ile322Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000276 in 1,087,952 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. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I322T) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 22)

Exomes 𝑓: 0.0000028 ( 0 hom. 1 hem. )

Consequence

AMMECR1
NM_015365.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.933

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=0.24970329).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
AMMECR1	NM_015365.3 link	c.966T>G	p.Ile322Met	missense_variant	Exon 6 of 6	ENST00000262844.10	NP_056180.1
AMMECR1	NM_001025580.2 link	c.855T>G	p.Ile285Met	missense_variant	Exon 5 of 5		NP_001020751.1
AMMECR1	NM_001171689.2 link	c.597T>G	p.Ile199Met	missense_variant	Exon 8 of 8		NP_001165160.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AMMECR1	ENST00000262844.10 link	c.966T>G	p.Ile322Met	missense_variant	Exon 6 of 6	1	NM_015365.3	ENSP00000262844.5		Q9Y4X0-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000276

AC:

AN:

1087952

Hom.:

Cov.:

AF XY:

0.00000282

AC XY:

AN XY:

355088

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26005

American (AMR)

AF:

0.00

AC:

AN:

34347

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18829

East Asian (EAS)

AF:

0.00

AC:

AN:

29924

South Asian (SAS)

AF:

0.00

AC:

AN:

52404

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40179

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4077

European-Non Finnish (NFE)

AF:

0.00000359

AC:

AN:

836544

Other (OTH)

AF:

0.00

AC:

AN:

45643

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Mar 07, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.966T>G (p.I322M) alteration is located in exon 6 (coding exon 6) of the AMMECR1 gene. This alteration results from a T to G substitution at nucleotide position 966, causing the isoleucine (I) at amino acid position 322 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Uncertain

0.15

BayesDel_noAF

Uncertain

-0.020

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.22

T;.;.

FATHMM_MKL

Uncertain

0.86

LIST_S2

Uncertain

0.87

D;D;D

M_CAP

Benign

0.0061

MetaRNN

Benign

0.25

T;T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

1.1

L;.;.

PhyloP100

0.93

PrimateAI

Uncertain

0.71

PROVEAN

Benign

-0.18

N;N;N

REVEL

Benign

0.24

Sift

Uncertain

0.014

D;D;T

Sift4G

Uncertain

0.023

D;D;T

Polyphen

0.99

D;D;.

Vest4

0.49

MutPred

0.20

Gain of solvent accessibility (P = 0.0365);.;.;

MVP

0.68

MPC

1.5

ClinPred

0.67

GERP RS

2.4

Varity_R

0.35

gMVP

0.69

Mutation Taster

=75/25

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-110198556-A-C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over