Variant X-110216604-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_015365.3(AMMECR1):c.613A>G(p.Met205Val) variant causes a missense change. The variant allele was found at a frequency of 0.000121 in 1,205,021 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 54 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., 5 hem., cov: 22)

Exomes 𝑓: 0.00012 ( 0 hom. 49 hem. )

Consequence

AMMECR1
NM_015365.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.96

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 links:

AMMECR1 (HGNC:):

AMMECR1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.117002666).

BS2

High Hemizygotes in GnomAd4 at 5 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
AMMECR1	NM_015365.3 linkuse as main transcript	c.613A>G	p.Met205Val	missense_variant	3/6	ENST00000262844.10	NP_056180.1
AMMECR1	NM_001025580.2 linkuse as main transcript	c.502A>G	p.Met168Val	missense_variant	2/5		NP_001020751.1
AMMECR1	NM_001171689.2 linkuse as main transcript	c.244A>G	p.Met82Val	missense_variant	5/8		NP_001165160.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AMMECR1	ENST00000262844.10 linkuse as main transcript	c.613A>G	p.Met205Val	missense_variant	3/6	1	NM_015365.3	ENSP00000262844.5		Q9Y4X0-1

Frequencies

GnomAD3 genomes

AF:

0.000107

AC:

AN:

111961

Hom.:

Cov.:

AF XY:

0.000146

AC XY:

AN XY:

34131

show subpopulations

Gnomad AFR

AF:

0.0000649

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000368

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000169

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000106

AC:

AN:

179975

Hom.:

AF XY:

0.000108

AC XY:

AN XY:

64603

show subpopulations

Gnomad AFR exome

AF:

0.000232

Gnomad AMR exome

AF:

0.000112

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000543

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000149

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000123

AC:

134

AN:

1093004

Hom.:

Cov.:

AF XY:

0.000137

AC XY:

AN XY:

358666

show subpopulations

Gnomad4 AFR exome

AF:

0.000114

Gnomad4 AMR exome

AF:

0.000114

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000332

Gnomad4 SAS exome

AF:

0.000224

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000130

Gnomad4 OTH exome

AF:

0.000109

GnomAD4 genome

AF:

0.000107

AC:

AN:

112017

Hom.:

Cov.:

AF XY:

0.000146

AC XY:

AN XY:

34197

show subpopulations

Gnomad4 AFR

AF:

0.0000648

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000369

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000169

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000225

Hom.:

Bravo

AF:

0.0000945

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000149

AC:

ExAC

AF:

0.0000659

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 19, 2024

The c.613A>G (p.M205V) alteration is located in exon 3 (coding exon 3) of the AMMECR1 gene. This alteration results from a A to G substitution at nucleotide position 613, causing the methionine (M) at amino acid position 205 to be replaced by a valine (V). 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

0.16

BayesDel_addAF

Benign

-0.0016

BayesDel_noAF

Uncertain

0.070

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.19

T;.;.

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.85

T;D;T

M_CAP

Benign

0.058

MetaRNN

Benign

0.12

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-1.0

N;.;.

PrimateAI

Pathogenic

0.82

PROVEAN

Benign

0.50

N;N;N

REVEL

Benign

0.19

Sift

Benign

0.12

T;T;T

Sift4G

Benign

0.13

T;T;T

Polyphen

0.024

B;B;.

Vest4

0.56

MVP

0.95

MPC

0.73

ClinPred

0.042

GERP RS

5.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.7

Varity_R

0.51

gMVP

0.89

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

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