X-110198562-A-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_015365.3(AMMECR1):c.960T>C(p.Asn320=) 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, single submitter B:1
• Conservation: PhyloP100: 3.75

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]

ACMG classification

Verdict is Benign. Variant got -10 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_single_submitter, 1 stars.
• BS2: High Hemizygotes in GnomAd at 75 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AMMECR1	NM_015365.3	c.960T>C	p.Asn320=	synonymous_variant	6/6	ENST00000262844.10
AMMECR1	NM_001025580.2	c.849T>C	p.Asn283=	synonymous_variant	5/5
AMMECR1	NM_001171689.2	c.591T>C	p.Asn197=	synonymous_variant	8/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AMMECR1	ENST00000262844.10	c.960T>C	p.Asn320=	synonymous_variant	6/6	1	NM_015365.3	A1

Frequencies

GnomAD3 genomes AF: 0.00276 AC: 308 AN: 111769 Hom.: 1 Cov.: 22 AF XY: 0.00221 AC XY: 75 AN XY: 33949

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

GnomAD3 exomes AF: 0.00284 AC: 478 AN: 168581 Hom.: 0 AF XY: 0.00273 AC XY: 149 AN XY: 54533

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 SAS 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

Gnomad4 AFR exome AF: 0.000770

Gnomad4 AMR exome AF: 0.000643

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00432

Gnomad4 NFE exome AF: 0.00645

Gnomad4 OTH exome AF: 0.00372

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

Gnomad4 AFR AF: 0.000358

Gnomad4 AMR AF: 0.000474

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00230

Gnomad4 NFE AF: 0.00520

Gnomad4 OTH AF: 0.000664

Alfa AF: 0.00342 Hom.: 29

Bravo AF: 0.00264

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
Cadd	Benign	7.2
Dann	Benign	0.64

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

Publications

LitVar

Other links and lift over

dbSNP: rs140247782; hg19: chrX-109441790;