chrX-110200911-A-T

Variant names:

• chrX-110200911-A-T
• rs7879645
• NM_015365.3:c.887+43T>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_015365.3(AMMECR1):​c.887+43T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0061 in 1,008,455 control chromosomes in the GnomAD database, including 219 homozygotes. There are 1,528 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., 864 hem., cov: 23)
  • Exomes 𝑓: 0.0032 (92 hom. 664 hem.)
• Consequence: AMMECR1 NM_015365.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.322
• 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant X-110200911-A-T is Benign according to our data. Variant chrX-110200911-A-T is described in ClinVar as [Benign]. Clinvar id is 1287673.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0994 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AMMECR1	NM_015365.3	c.887+43T>A		intron_variant	Intron 5 of 5	ENST00000262844.10	NP_056180.1
AMMECR1	NM_001025580.2	c.776+43T>A		intron_variant	Intron 4 of 4		NP_001020751.1
AMMECR1	NM_001171689.2	c.518+43T>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+43T>A		intron_variant	Intron 5 of 5	1	NM_015365.3	ENSP00000262844.5

Frequencies

GnomAD3 genomes AF: 0.0293 AC: 3283 AN: 112001 Hom.: 127 Cov.: 23

Gnomad AFR AF: 0.102

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00869

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000372

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000132

Gnomad OTH AF: 0.0233

GnomAD2 exomes AF: 0.00882 AC: 1500 AN: 170133 AF XY: 0.00572

Gnomad AFR exome AF: 0.104

Gnomad AMR exome AF: 0.00494

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000516

Gnomad OTH exome AF: 0.00405

GnomAD4 exome AF: 0.00319 AC: 2861 AN: 896401 Hom.: 92 Cov.: 13 AF XY: 0.00263 AC XY: 664 AN XY: 252187

African (AFR) AF: 0.103 AC: 2297 AN: 22297

American (AMR) AF: 0.00611 AC: 208 AN: 34027

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17612

East Asian (EAS) AF: 0.00 AC: 0 AN: 29218

South Asian (SAS) AF: 0.000473 AC: 23 AN: 48644

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39050

Middle Eastern (MID) AF: 0.00244 AC: 9 AN: 3681

European-Non Finnish (NFE) AF: 0.0000513 AC: 34 AN: 662563

Other (OTH) AF: 0.00738 AC: 290 AN: 39309

GnomAD4 genome AF: 0.0294 AC: 3291 AN: 112054 Hom.: 127 Cov.: 23 AF XY: 0.0252 AC XY: 864 AN XY: 34270

African (AFR) AF: 0.102 AC: 3156 AN: 30831

American (AMR) AF: 0.00868 AC: 92 AN: 10604

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2645

East Asian (EAS) AF: 0.00 AC: 0 AN: 3582

South Asian (SAS) AF: 0.000373 AC: 1 AN: 2682

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6133

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 218

European-Non Finnish (NFE) AF: 0.000132 AC: 7 AN: 53160

Other (OTH) AF: 0.0230 AC: 35 AN: 1520

Alfa AF: 0.0160 Hom.: 73

Bravo AF: 0.0345

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

May 20, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.31
DANN	Benign	0.72
PhyloP100		-0.32
Mutation Taster		=100/0	polymorphism (auto)

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: rs7879645; hg19: chrX-109444139;