X-110202286-G-A

Variant names:

• chrX-110202286-G-A
• rs141830389
• NM_015365.3:c.790+160C>T

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.790+160C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0273 in 112,150 control chromosomes in the GnomAD database, including 100 homozygotes. There are 855 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.027 (100 hom., 855 hem., cov: 23)
• Consequence: AMMECR1 NM_015365.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.97
• 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=-0.92).
• BP6: Variant X-110202286-G-A is Benign according to our data. Variant chrX-110202286-G-A is described in ClinVar as [Benign]. Clinvar id is 1263366.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.091 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AMMECR1	NM_015365.3	c.790+160C>T		intron_variant	Intron 4 of 5	ENST00000262844.10	NP_056180.1
AMMECR1	NM_001025580.2	c.679+160C>T		intron_variant	Intron 3 of 4		NP_001020751.1
AMMECR1	NM_001171689.2	c.421+160C>T		intron_variant	Intron 6 of 7		NP_001165160.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AMMECR1	ENST00000262844.10	c.790+160C>T		intron_variant	Intron 4 of 5	1	NM_015365.3	ENSP00000262844.5

Frequencies

GnomAD3 genomes AF: 0.0273 AC: 3055 AN: 112098 Hom.: 98 Cov.: 23

Gnomad AFR AF: 0.0939

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0111

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000301

Gnomad OTH AF: 0.0173

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

GnomAD4 genome AF: 0.0273 AC: 3060 AN: 112150 Hom.: 100 Cov.: 23 AF XY: 0.0249 AC XY: 855 AN XY: 34404

African (AFR) AF: 0.0939 AC: 2901 AN: 30911

American (AMR) AF: 0.0110 AC: 117 AN: 10632

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 3594

South Asian (SAS) AF: 0.00 AC: 0 AN: 2707

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6104

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 217

European-Non Finnish (NFE) AF: 0.000301 AC: 16 AN: 53135

Other (OTH) AF: 0.0171 AC: 26 AN: 1521

Alfa AF: 0.0218 Hom.: 65

Bravo AF: 0.0320

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

May 20, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.0020
DANN	Benign	0.44
PhyloP100		-2.0
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: rs141830389; hg19: chrX-109445514;