Genetic Variant AMMECR1:c.887+44G>A (chrX-110200910-C-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_015365.3(AMMECR1):c.887+44G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000159 in 882,610 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 5 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 23)

Exomes 𝑓: 0.000016 ( 0 hom. 5 hem. )

Consequence

AMMECR1
NM_015365.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.216

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: Labcorp Genetics (formerly Invitae), Illumina
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: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BS2

High Hemizygotes in GnomAdExome4 at 5 XL gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015365.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
AMMECR1	NM_015365.3	MANE Select	c.887+44G>A	intron	N/A	NP_056180.1	Q9Y4X0-1
AMMECR1	NM_001025580.2		c.776+44G>A	intron	N/A	NP_001020751.1	Q9Y4X0-3
AMMECR1	NM_001171689.2		c.518+44G>A	intron	N/A	NP_001165160.1	Q9Y4X0-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
AMMECR1	ENST00000262844.10	TSL:1 MANE Select	c.887+44G>A	intron	N/A	ENSP00000262844.5	Q9Y4X0-1
AMMECR1	ENST00000372059.6	TSL:1	c.776+44G>A	intron	N/A	ENSP00000361129.2	Q9Y4X0-3
AMMECR1	ENST00000686065.1		c.887+44G>A	intron	N/A	ENSP00000509935.1	A0A8I5KSJ4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000591

AC:

AN:

169065

AF XY:

0.0000180

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000700

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000159

AC:

AN:

882610

Hom.:

Cov.:

AF XY:

0.0000204

AC XY:

AN XY:

245676

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

22040

American (AMR)

AF:

0.00

AC:

AN:

33846

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

17459

East Asian (EAS)

AF:

0.00

AC:

AN:

29147

South Asian (SAS)

AF:

0.00

AC:

AN:

48086

European-Finnish (FIN)

AF:

0.0000514

AC:

AN:

38916

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3634

European-Non Finnish (NFE)

AF:

0.0000184

AC:

AN:

650662

Other (OTH)

AF:

0.00

AC:

AN:

38820

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.39

(source)

DANN

Benign

0.39

PhyloP100

-0.22

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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over