X-64192215-G-C

Position:

• chrX-64192215-G-C

Variant summary

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

The NM_152424.4(AMER1):​c.1072C>G​(p.Arg358Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 24)
• Consequence: AMER1 NM_152424.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.192

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	Protein	UniProt
AMER1	NM_152424.4	c.1072C>G	p.Arg358Gly	missense_variant	2/2	ENST00000374869.8	NP_689637.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AMER1	ENST00000374869.8	c.1072C>G	p.Arg358Gly	missense_variant	2/2	5	NM_152424.4	ENSP00000364003	P1

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 24

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.96
BayesDel_addAF	Uncertain	0.10	D
BayesDel_noAF	Benign	-0.090
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.33	T;T
FATHMM_MKL	Benign	0.42	N
LIST_S2	Uncertain	0.87	.;D
M_CAP	Benign	0.016	T
MetaRNN	Uncertain	0.61	D;D
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.4	M;M
MutationTaster	Benign	0.92	D;D;D
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-2.1	N;N
REVEL	Benign	0.24
Sift	Uncertain	0.0090	D;D
Sift4G	Uncertain	0.018	D;D
Polyphen		0.83	P;P
Vest4		0.72
MutPred		0.41		Gain of ubiquitination at K357 (P = 0.0338);Gain of ubiquitination at K357 (P = 0.0338);
MVP		0.64
MPC		0.22
ClinPred		0.96	D
GERP RS		1.2
Varity_R		0.67
gMVP		0.42

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-63412095;