X-112779403-A-G

Position:

• chrX-112779403-A-G

Variant summary

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

The NM_001113490.2(AMOT):​c.2751T>C​(p.Ala917Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000316 in 949,781 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 3 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 22)
  • Exomes 𝑓: 0.0000032 (0 hom. 3 hem.)
• Consequence: AMOT NM_001113490.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.234

Genes affected

AMOT (HGNC:17810): (angiomotin) This gene belongs to the motin family of angiostatin binding proteins characterized by conserved coiled-coil domains and C-terminal PDZ binding motifs. The encoded protein is expressed predominantly in endothelial cells of capillaries as well as larger vessels of the placenta where it may mediate the inhibitory effect of angiostatin on tube formation and the migration of endothelial cells toward growth factors during the formation of new blood vessels. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant X-112779403-A-G is Benign according to our data. Variant chrX-112779403-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2661223.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.234 with no splicing effect.
• BS2: High Hemizygotes in GnomAdExome4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AMOT	NM_001113490.2	c.2751T>C	p.Ala917Ala	synonymous_variant	13/14	ENST00000371959.9	NP_001106962.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AMOT	ENST00000371959.9	c.2751T>C	p.Ala917Ala	synonymous_variant	13/14	1	NM_001113490.2	ENSP00000361027.3
AMOT	ENST00000371962.5	c.2055T>C	p.Ala685Ala	synonymous_variant	10/11	1		ENSP00000361030.1
AMOT	ENST00000304758.5	c.1524T>C	p.Ala508Ala	synonymous_variant	11/12	1		ENSP00000305557.1

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome AF: 0.00000316 AC: 3 AN: 949781 Hom.: 0 Cov.: 22 AF XY: 0.0000103 AC XY: 3 AN XY: 290651

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000205

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000138

Gnomad4 OTH exome AF: 0.0000245

GnomAD4 genome Cov.: 22

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

May 01, 2023

AMOT: PM2:Supporting, BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.1
DANN	Benign	0.65

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: rs760467274; hg19: chrX-112022631;