rs587778022

Positions:

• chrX-64192124-ACCTCTTCTT-A
• chrX-64192124-ACCTCTTCTT-ACCTCTTCTTCCTCTTCTT

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_152424.4(AMER1):​c.1154_1162delAAGAAGAGG​(p.Glu385_Glu387del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000417 in 1,204,948 control chromosomes in the GnomAD database, including 1 homozygotes. There are 178 hemizygotes in GnomAD. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00049 (0 hom., 20 hem., cov: 23)
  • Exomes 𝑓: 0.00041 (1 hom. 158 hem.)
• Consequence: AMER1 NM_152424.4 disruptive_inframe_deletion
• Clinical Significance: Benign criteria provided, single submitter B:1 O:1
• Conservation: PhyloP100: 3.34

Genes affected

AMER1 (HGNC:26837): (APC membrane recruitment protein 1) The protein encoded by this gene upregulates trancriptional activation by the Wilms tumor protein and interacts with many other proteins, including CTNNB1, APC, AXIN1, and AXIN2. Defects in this gene are a cause of osteopathia striata with cranial sclerosis (OSCS). [provided by RefSeq, May 2010]

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP6: Variant X-64192124-ACCTCTTCTT-A is Benign according to our data. Variant chrX-64192124-ACCTCTTCTT-A is described in ClinVar as [Benign]. Clinvar id is 133486.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Hemizygotes in GnomAd4 at 20 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AMER1	NM_152424.4	c.1154_1162delAAGAAGAGG	p.Glu385_Glu387del	disruptive_inframe_deletion	2/2	ENST00000374869.8	NP_689637.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AMER1	ENST00000374869.8	c.1154_1162delAAGAAGAGG	p.Glu385_Glu387del	disruptive_inframe_deletion	2/2	5	NM_152424.4	ENSP00000364003.4

Frequencies

GnomAD3 genomes AF: 0.000489 AC: 53 AN: 108351 Hom.: 0 Cov.: 23 AF XY: 0.000635 AC XY: 20 AN XY: 31499

Gnomad AFR AF: 0.0000338

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000978

Gnomad ASJ AF: 0.0172

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000116

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000852 AC: 156 AN: 183206 Hom.: 2 AF XY: 0.000901 AC XY: 61 AN XY: 67684

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000365

Gnomad ASJ exome AF: 0.0183

Gnomad EAS exome AF: 0.0000722

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000183

Gnomad OTH exome AF: 0.000442

GnomAD4 exome AF: 0.000410 AC: 450 AN: 1096597 Hom.: 1 AF XY: 0.000436 AC XY: 158 AN XY: 362007

Gnomad4 AFR exome AF: 0.0000379

Gnomad4 AMR exome AF: 0.0000284

Gnomad4 ASJ exome AF: 0.0174

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000797

Gnomad4 OTH exome AF: 0.000934

GnomAD4 genome AF: 0.000489 AC: 53 AN: 108351 Hom.: 0 Cov.: 23 AF XY: 0.000635 AC XY: 20 AN XY: 31499

Gnomad4 AFR AF: 0.0000338

Gnomad4 AMR AF: 0.0000978

Gnomad4 ASJ AF: 0.0172

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000116

Gnomad4 OTH AF: 0.00

Alfa AF: 0.00252 Hom.: 17

Bravo AF: 0.000536

ClinVar

Significance: Benign

Submissions summary: Benign:1 Other:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 23, 2023

- -

not specified Other:1

not provided, no classification provided

reference population

ITMI

Sep 19, 2013

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs587778022; hg19: chrX-63412004;