X-110200910-C-T

Variant names:

• chrX-110200910-C-T
• rs7879171
• NM_015365.3:c.887+44G>A

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.216
• Publications: 0 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: Illumina, Labcorp Genetics (formerly Invitae)
• Alport syndrome-intellectual disability-midface hypoplasia-elliptocytosis syndrome

  Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AMMECR1	NM_015365.3	c.887+44G>A		intron_variant	Intron 5 of 5	ENST00000262844.10	NP_056180.1
AMMECR1	NM_001025580.2	c.776+44G>A		intron_variant	Intron 4 of 4		NP_001020751.1
AMMECR1	NM_001171689.2	c.518+44G>A		intron_variant	Intron 7 of 7		NP_001165160.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AMMECR1	ENST00000262844.10	c.887+44G>A		intron_variant	Intron 5 of 5	1	NM_015365.3	ENSP00000262844.5

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD2 exomes AF: 0.00000591 AC: 1 AN: 169065 AF XY: 0.0000180

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: 14 AN: 882610 Hom.: 0 Cov.: 13 AF XY: 0.0000204 AC XY: 5 AN XY: 245676

African (AFR) AF: 0.00 AC: 0 AN: 22040

American (AMR) AF: 0.00 AC: 0 AN: 33846

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17459

East Asian (EAS) AF: 0.00 AC: 0 AN: 29147

South Asian (SAS) AF: 0.00 AC: 0 AN: 48086

European-Finnish (FIN) AF: 0.0000514 AC: 2 AN: 38916

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3634

European-Non Finnish (NFE) AF: 0.0000184 AC: 12 AN: 650662

Other (OTH) AF: 0.00 AC: 0 AN: 38820

GnomAD4 genome Cov.: 23

Alfa AF: 0.00 Hom.: 20

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.39
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

Other links and lift over

dbSNP: rs7879171; hg19: chrX-109444138;