X-110200910-C-A

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: Labcorp Genetics (formerly Invitae), Illumina
• 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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015365.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AMMECR1	NM_015365.3	MANE Select	c.887+44G>T		intron	N/A	NP_056180.1	Q9Y4X0-1
	AMMECR1	NM_001025580.2		c.776+44G>T		intron	N/A	NP_001020751.1	Q9Y4X0-3
	AMMECR1	NM_001171689.2		c.518+44G>T		intron	N/A	NP_001165160.1	Q9Y4X0-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AMMECR1	ENST00000262844.10	TSL:1 MANE Select	c.887+44G>T		intron	N/A	ENSP00000262844.5	Q9Y4X0-1
	AMMECR1	ENST00000372059.6	TSL:1	c.776+44G>T		intron	N/A	ENSP00000361129.2	Q9Y4X0-3
	AMMECR1	ENST00000686065.1		c.887+44G>T		intron	N/A	ENSP00000509935.1	A0A8I5KSJ4

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

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

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;