X-110200910-C-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_015365.3(AMMECR1):c.887+44G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00619 in 994,453 control chromosomes in the GnomAD database, including 221 homozygotes. There are 1,532 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.029 (127 hom., 868 hem., cov: 23)
  • Exomes 𝑓: 0.0032 (94 hom. 664 hem.)
• Consequence: AMMECR1 NM_015365.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.216

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant X-110200910-C-A is Benign according to our data. Variant chrX-110200910-C-A is described in ClinVar as [Benign]. Clinvar id is 1285799.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0997 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AMMECR1	NM_015365.3	c.887+44G>T		intron_variant		ENST00000262844.10
AMMECR1	NM_001025580.2	c.776+44G>T		intron_variant
AMMECR1	NM_001171689.2	c.518+44G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AMMECR1	ENST00000262844.10	c.887+44G>T		intron_variant		1	NM_015365.3	A1

Frequencies

GnomAD3 genomes AF: 0.0294 AC: 3287 AN: 111809 Hom.: 127 Cov.: 23 AF XY: 0.0254 AC XY: 863 AN XY: 34033

Gnomad AFR AF: 0.103

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00871

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000373

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000151

Gnomad OTH AF: 0.0234

GnomAD3 exomes AF: 0.00884 AC: 1494 AN: 169065 Hom.: 51 AF XY: 0.00571 AC XY: 317 AN XY: 55537

Gnomad AFR exome AF: 0.104

Gnomad AMR exome AF: 0.00488

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000258

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000519

Gnomad OTH exome AF: 0.00408

GnomAD4 exome AF: 0.00324 AC: 2856 AN: 882589 Hom.: 94 Cov.: 13 AF XY: 0.00270 AC XY: 664 AN XY: 245667

Gnomad4 AFR exome AF: 0.104

Gnomad4 AMR exome AF: 0.00615

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000499

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000538

Gnomad4 OTH exome AF: 0.00750

GnomAD4 genome AF: 0.0295 AC: 3295 AN: 111864 Hom.: 127 Cov.: 23 AF XY: 0.0255 AC XY: 868 AN XY: 34096

Gnomad4 AFR AF: 0.103

Gnomad4 AMR AF: 0.00869

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000374

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000151

Gnomad4 OTH AF: 0.0231

Alfa AF: 0.00424 Hom.: 20

Bravo AF: 0.0345

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 20, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	0.32
Dann	Benign	0.54

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

LitVar

Other links and lift over

dbSNP: rs7879171; hg19: chrX-109444138;