X-110309439-C-T

Variant names:

• chrX-110309439-C-T
• rs2294504
• NM_015365.3:c.473+8160G>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_015365.3(AMMECR1):​c.473+8160G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.281 in 111,208 control chromosomes in the GnomAD database, including 4,370 homozygotes. There are 9,667 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.28 (4370 hom., 9667 hem., cov: 22)
  • Exomes 𝑓: 0.0 (0 hom. 0 hem.)
  • Failed GnomAD Quality Control
• Consequence: AMMECR1 NM_015365.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.693
• Publications: 4 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.26).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.902 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.473+8160G>A		intron	N/A	NP_056180.1	Q9Y4X0-1
	AMMECR1	NM_001025580.2		c.473+8160G>A		intron	N/A	NP_001020751.1	Q9Y4X0-3
	AMMECR1	NM_001171689.2		c.104+8160G>A		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.473+8160G>A		intron	N/A	ENSP00000262844.5	Q9Y4X0-1
	AMMECR1	ENST00000372059.6	TSL:1	c.473+8160G>A		intron	N/A	ENSP00000361129.2	Q9Y4X0-3
	AMMECR1	ENST00000686065.1		c.473+8160G>A		intron	N/A	ENSP00000509935.1	A0A8I5KSJ4

Frequencies

GnomAD3 genomes AF: 0.281 AC: 31263 AN: 111160 Hom.: 4365 Cov.: 22

Gnomad AFR AF: 0.0514

Gnomad AMI AF: 0.480

Gnomad AMR AF: 0.429

Gnomad ASJ AF: 0.224

Gnomad EAS AF: 0.929

Gnomad SAS AF: 0.603

Gnomad FIN AF: 0.330

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.321

Gnomad OTH AF: 0.286

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 2 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 2

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1

Other (OTH) AF: 0.00 AC: 0 AN: 1

GnomAD4 genome AF: 0.281 AC: 31264 AN: 111208 Hom.: 4370 Cov.: 22 AF XY: 0.289 AC XY: 9667 AN XY: 33430

African (AFR) AF: 0.0513 AC: 1578 AN: 30754

American (AMR) AF: 0.429 AC: 4524 AN: 10549

Ashkenazi Jewish (ASJ) AF: 0.224 AC: 591 AN: 2637

East Asian (EAS) AF: 0.928 AC: 3252 AN: 3503

South Asian (SAS) AF: 0.603 AC: 1582 AN: 2624

European-Finnish (FIN) AF: 0.330 AC: 1934 AN: 5867

Middle Eastern (MID) AF: 0.246 AC: 52 AN: 211

European-Non Finnish (NFE) AF: 0.321 AC: 16980 AN: 52877

Other (OTH) AF: 0.296 AC: 446 AN: 1509

Alfa AF: 0.325 Hom.: 10206

Bravo AF: 0.285

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.26
CADD	Benign	17
DANN	Benign	0.80
PhyloP100		0.69
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: rs2294504; hg19: chrX-109552667;