rs2294504

Variant names:

• chrX-110309439-C-A
• rs2294504
• NM_015365.3:c.473+8160G>T

Your query was ambiguous. Multiple possible variants found:

• chrX-110309439-C-A
• chrX-110309439-C-G
• chrX-110309439-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_015365.3(AMMECR1):​c.473+8160G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 22)
• Consequence: AMMECR1 NM_015365.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.693
• Publications: 4 publications found

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

ACMG classification

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 (BayesDel_noAF=-0.25).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AMMECR1	NM_015365.3	MANE Select	c.473+8160G>T		intron	N/A	NP_056180.1	Q9Y4X0-1
	AMMECR1	NM_001025580.2		c.473+8160G>T		intron	N/A	NP_001020751.1	Q9Y4X0-3
	AMMECR1	NM_001171689.2		c.104+8160G>T		intron	N/A	NP_001165160.1	Q9Y4X0-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AMMECR1	ENST00000262844.10	TSL:1 MANE Select	c.473+8160G>T		intron	N/A	ENSP00000262844.5	Q9Y4X0-1
	AMMECR1	ENST00000372059.6	TSL:1	c.473+8160G>T		intron	N/A	ENSP00000361129.2	Q9Y4X0-3
	AMMECR1	ENST00000686065.1		c.473+8160G>T		intron	N/A	ENSP00000509935.1	A0A8I5KSJ4

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 22

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.25
CADD	Benign	16
DANN	Benign	0.79
PhyloP100		0.69

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

Other links and lift over

dbSNP: rs2294504; hg19: chrX-109552667;