chrX-64189910-G-A

Position:

• chrX-64189910-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_152424.4(AMER1):​c.3377C>T​(p.Ser1126Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 21)
• Consequence: AMER1 NM_152424.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.61

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AMER1	NM_152424.4	c.3377C>T	p.Ser1126Phe	missense_variant	2/2	ENST00000374869.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AMER1	ENST00000374869.8	c.3377C>T	p.Ser1126Phe	missense_variant	2/2	5	NM_152424.4	P1

Frequencies

GnomAD3 genomes Cov.: 21

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 21

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Invitae

Oct 03, 2023

This sequence change replaces serine, which is neutral and polar, with phenylalanine, which is neutral and non-polar, at codon 1126 of the AMER1 protein (p.Ser1126Phe). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with AMER1-related conditions. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.040
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.34	T;T
FATHMM_MKL	Uncertain	0.92	D
M_CAP	Uncertain	0.085	D
MetaRNN	Uncertain	0.43	T;T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	1.9	L;L
MutationTaster	Benign	1.0	D;D;N
PrimateAI	Benign	0.43	T
Polyphen		1.0	D;D
Vest4		0.61
MutPred		0.21		Loss of disorder (P = 0.0313);Loss of disorder (P = 0.0313);
MVP		0.79
MPC		0.16
ClinPred		0.83	D
GERP RS		4.0
Varity_R		0.20
gMVP		0.34

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

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-63409790;