NM_015365.3:c.960T>C

Variant names:

• chrX-110198562-A-G
• rs140247782
• NM_015365.3:c.960T>C

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_015365.3(AMMECR1):​c.960T>C​(p.Asn320Asn) variant causes a synonymous change. The variant allele was found at a frequency of 0.00508 in 1,200,325 control chromosomes in the GnomAD database, including 9 homozygotes. There are 1,858 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0028 (1 hom., 75 hem., cov: 22)
  • Exomes 𝑓: 0.0053 (8 hom. 1783 hem.)
• Consequence: AMMECR1 NM_015365.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 3.75
• Publications: 1 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 -16 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BP6: Variant X-110198562-A-G is Benign according to our data. Variant chrX-110198562-A-G is described in ClinVar as [Benign]. Clinvar id is 779292.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Hemizygotes in GnomAd4 at 75 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AMMECR1	NM_015365.3	c.960T>C	p.Asn320Asn	synonymous_variant	Exon 6 of 6	ENST00000262844.10	NP_056180.1
AMMECR1	NM_001025580.2	c.849T>C	p.Asn283Asn	synonymous_variant	Exon 5 of 5		NP_001020751.1
AMMECR1	NM_001171689.2	c.591T>C	p.Asn197Asn	synonymous_variant	Exon 8 of 8		NP_001165160.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AMMECR1	ENST00000262844.10	c.960T>C	p.Asn320Asn	synonymous_variant	Exon 6 of 6	1	NM_015365.3	ENSP00000262844.5

Frequencies

GnomAD3 genomes AF: 0.00276 AC: 308 AN: 111769 Hom.: 1 Cov.: 22

Gnomad AFR AF: 0.000358

Gnomad AMI AF: 0.00146

Gnomad AMR AF: 0.000474

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00230

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00520

Gnomad OTH AF: 0.000664

GnomAD2 exomes AF: 0.00284 AC: 478 AN: 168581 AF XY: 0.00273

Gnomad AFR exome AF: 0.000636

Gnomad AMR exome AF: 0.000510

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00332

Gnomad NFE exome AF: 0.00517

Gnomad OTH exome AF: 0.00342

GnomAD4 exome AF: 0.00532 AC: 5788 AN: 1088556 Hom.: 8 Cov.: 28 AF XY: 0.00502 AC XY: 1783 AN XY: 355384

African (AFR) AF: 0.000770 AC: 20 AN: 25969

American (AMR) AF: 0.000643 AC: 22 AN: 34207

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18880

East Asian (EAS) AF: 0.00 AC: 0 AN: 29893

South Asian (SAS) AF: 0.00 AC: 0 AN: 52549

European-Finnish (FIN) AF: 0.00432 AC: 174 AN: 40237

Middle Eastern (MID) AF: 0.000246 AC: 1 AN: 4069

European-Non Finnish (NFE) AF: 0.00645 AC: 5401 AN: 837097

Other (OTH) AF: 0.00372 AC: 170 AN: 45655

GnomAD4 genome AF: 0.00276 AC: 308 AN: 111769 Hom.: 1 Cov.: 22 AF XY: 0.00221 AC XY: 75 AN XY: 33949

African (AFR) AF: 0.000358 AC: 11 AN: 30737

American (AMR) AF: 0.000474 AC: 5 AN: 10553

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2648

East Asian (EAS) AF: 0.00 AC: 0 AN: 3553

South Asian (SAS) AF: 0.00 AC: 0 AN: 2659

European-Finnish (FIN) AF: 0.00230 AC: 14 AN: 6078

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 238

European-Non Finnish (NFE) AF: 0.00520 AC: 276 AN: 53109

Other (OTH) AF: 0.000664 AC: 1 AN: 1507

Alfa AF: 0.00342 Hom.: 29

Bravo AF: 0.00264

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

- -

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

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	-0.52
CADD	Benign	7.2
DANN	Benign	0.64
PhyloP100		3.7
Mutation Taster		=91/9	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: rs140247782; hg19: chrX-109441790;