chrX-110264538-AAGTACCT-GATTAC

Position:

• chrX-110264538-AAGTACCT-GATTAC

Variant summary

Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1 PM2

The NM_015365.3(AMMECR1):​c.528_535delAGGTACTTinsGTAATC​(p.Ile176fs) variant causes a frameshift, stop gained, missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 22)
• Consequence: AMMECR1 NM_015365.3 frameshift, stop_gained, missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.92

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 (HGNC:):

ACMG classification

Verdict is Pathogenic. Variant got 10 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AMMECR1	NM_015365.3	c.528_535delAGGTACTTinsGTAATC	p.Ile176fs	frameshift_variant, stop_gained, missense_variant	2/6	ENST00000262844.10	NP_056180.1
AMMECR1	NM_001171689.2	c.159_166delAGGTACTTinsGTAATC	p.Ile53fs	frameshift_variant, stop_gained, missense_variant	4/8		NP_001165160.1
AMMECR1	NM_001025580.2	c.474-47913_474-47906delAGGTACTTinsGTAATC		intron_variant			NP_001020751.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AMMECR1	ENST00000262844.10	c.528_535delAGGTACTTinsGTAATC	p.Ile176fs	frameshift_variant, stop_gained, missense_variant	2/6	1	NM_015365.3	ENSP00000262844.5

Frequencies

GnomAD3 genomes Cov.: 22

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 22

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Aug 01, 2023

AMMECR1: PM2, PVS1:Moderate -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-109507766;