X-110202486-T-C

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_015365.3(AMMECR1):c.750A>G(p.Lys250=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000306 in 1,207,759 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 85 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0018 (0 hom., 52 hem., cov: 23)
  • Exomes 𝑓: 0.00015 (0 hom. 33 hem.)
• Consequence: AMMECR1 NM_015365.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.12

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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BP6: Variant X-110202486-T-C is Benign according to our data. Variant chrX-110202486-T-C is described in ClinVar as [Benign]. Clinvar id is 746580.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=1.12 with no splicing effect.
• BS2: High Hemizygotes in GnomAd at 52 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AMMECR1	NM_015365.3	c.750A>G	p.Lys250=	synonymous_variant	4/6	ENST00000262844.10
AMMECR1	NM_001025580.2	c.639A>G	p.Lys213=	synonymous_variant	3/5
AMMECR1	NM_001171689.2	c.381A>G	p.Lys127=	synonymous_variant	6/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AMMECR1	ENST00000262844.10	c.750A>G	p.Lys250=	synonymous_variant	4/6	1	NM_015365.3	A1

Frequencies

GnomAD3 genomes AF: 0.00181 AC: 203 AN: 111936 Hom.: 0 Cov.: 23 AF XY: 0.00152 AC XY: 52 AN XY: 34158

Gnomad AFR AF: 0.00607

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000851

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000566

Gnomad OTH AF: 0.00264

GnomAD3 exomes AF: 0.000527 AC: 96 AN: 182199 Hom.: 0 AF XY: 0.000298 AC XY: 20 AN XY: 67019

Gnomad AFR exome AF: 0.00641

Gnomad AMR exome AF: 0.000405

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000123

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000151 AC: 165 AN: 1095768 Hom.: 0 Cov.: 28 AF XY: 0.0000912 AC XY: 33 AN XY: 361824

Gnomad4 AFR exome AF: 0.00483

Gnomad4 AMR exome AF: 0.000485

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000952

Gnomad4 OTH exome AF: 0.000283

GnomAD4 genome AF: 0.00183 AC: 205 AN: 111991 Hom.: 0 Cov.: 23 AF XY: 0.00152 AC XY: 52 AN XY: 34223

Gnomad4 AFR AF: 0.00612

Gnomad4 AMR AF: 0.000850

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000566

Gnomad4 OTH AF: 0.00260

Alfa AF: 0.000868 Hom.: 4

Bravo AF: 0.00183

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

May 14, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
Cadd	Benign	10
Dann	Benign	0.68

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: rs140856361; hg19: chrX-109445714;