NM_015365.3:c.887+44G>T

Variant names:

• chrX-110200910-C-A
• rs7879171
• NM_015365.3:c.887+44G>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.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, multiple submitters, no conflicts B:2
• 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 -20 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_multiple_submitters_no_conflicts, 2 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 rank	MANE	Protein	UniProt
AMMECR1	NM_015365.3	c.887+44G>T		intron_variant	Intron 5 of 5	ENST00000262844.10	NP_056180.1
AMMECR1	NM_001025580.2	c.776+44G>T		intron_variant	Intron 4 of 4		NP_001020751.1
AMMECR1	NM_001171689.2	c.518+44G>T		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>T		intron_variant	Intron 5 of 5	1	NM_015365.3	ENSP00000262844.5

Frequencies

GnomAD3 genomes AF: 0.0294 AC: 3287 AN: 111809 Hom.: 127 Cov.: 23

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

GnomAD2 exomes AF: 0.00884 AC: 1494 AN: 169065 AF XY: 0.00571

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 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

African (AFR) AF: 0.104 AC: 2289 AN: 22024

American (AMR) AF: 0.00615 AC: 208 AN: 33843

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

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

South Asian (SAS) AF: 0.000499 AC: 24 AN: 48084

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 38916

Middle Eastern (MID) AF: 0.00248 AC: 9 AN: 3634

European-Non Finnish (NFE) AF: 0.0000538 AC: 35 AN: 650662

Other (OTH) AF: 0.00750 AC: 291 AN: 38820

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

African (AFR) AF: 0.103 AC: 3159 AN: 30763

American (AMR) AF: 0.00869 AC: 92 AN: 10581

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2650

East Asian (EAS) AF: 0.00 AC: 0 AN: 3575

South Asian (SAS) AF: 0.000374 AC: 1 AN: 2673

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6099

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

European-Non Finnish (NFE) AF: 0.000151 AC: 8 AN: 53115

Other (OTH) AF: 0.0231 AC: 35 AN: 1512

Alfa AF: 0.00424 Hom.: 20

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

-

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	-0.82
CADD	Benign	0.32
DANN	Benign	0.54
PhyloP100		-0.22
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: rs7879171; hg19: chrX-109444138;