chrX-112779131-G-A

Variant names:

• chrX-112779131-G-A
• rs764543196
• NM_001113490.2:c.3023C>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Moderate BP6_Moderate BS2

The NM_001113490.2(AMOT):​c.3023C>T​(p.Pro1008Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000918 in 1,089,366 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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0000089 (0 hom., 1 hem., cov: 23)
  • Exomes 𝑓: 0.0000092 (0 hom. 2 hem.)
• Consequence: AMOT NM_001113490.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.02
• Publications: 0 publications found

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

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.1632461).
• BP6: Variant X-112779131-G-A is Benign according to our data. Variant chrX-112779131-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2661222.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Hemizygotes in GnomAdExome4 at 2 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001113490.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AMOT	NM_001113490.2	MANE Select	c.3023C>T	p.Pro1008Leu	missense	Exon 13 of 14	NP_001106962.1	Q4VCS5-1
	AMOT	NM_001386998.1		c.3023C>T	p.Pro1008Leu	missense	Exon 14 of 15	NP_001373927.1	Q4VCS5-1
	AMOT	NM_001386999.1		c.3023C>T	p.Pro1008Leu	missense	Exon 13 of 14	NP_001373928.1	Q4VCS5-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AMOT	ENST00000371959.9	TSL:1 MANE Select	c.3023C>T	p.Pro1008Leu	missense	Exon 13 of 14	ENSP00000361027.3	Q4VCS5-1
	AMOT	ENST00000371962.5	TSL:1	c.2327C>T	p.Pro776Leu	missense	Exon 10 of 11	ENSP00000361030.1	E7ERM3
	AMOT	ENST00000304758.5	TSL:1	c.1796C>T	p.Pro599Leu	missense	Exon 11 of 12	ENSP00000305557.1	Q4VCS5-2

Frequencies

GnomAD3 genomes AF: 0.00000894 AC: 1 AN: 111816 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000188

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000276 AC: 5 AN: 181262 AF XY: 0.0000298

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000365

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000723

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000251

Gnomad OTH exome AF: 0.000222

GnomAD4 exome AF: 0.00000921 AC: 9 AN: 977550 Hom.: 0 Cov.: 21 AF XY: 0.00000722 AC XY: 2 AN XY: 276904

African (AFR) AF: 0.0000832 AC: 2 AN: 24044

American (AMR) AF: 0.0000285 AC: 1 AN: 35085

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18653

East Asian (EAS) AF: 0.00 AC: 0 AN: 29721

South Asian (SAS) AF: 0.0000194 AC: 1 AN: 51608

European-Finnish (FIN) AF: 0.0000247 AC: 1 AN: 40497

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3863

European-Non Finnish (NFE) AF: 0.00000546 AC: 4 AN: 731936

Other (OTH) AF: 0.00 AC: 0 AN: 42143

GnomAD4 genome AF: 0.00000894 AC: 1 AN: 111816 Hom.: 0 Cov.: 23 AF XY: 0.0000294 AC XY: 1 AN XY: 33988

African (AFR) AF: 0.00 AC: 0 AN: 30706

American (AMR) AF: 0.00 AC: 0 AN: 10512

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2652

East Asian (EAS) AF: 0.00 AC: 0 AN: 3572

South Asian (SAS) AF: 0.00 AC: 0 AN: 2639

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6127

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 240

European-Non Finnish (NFE) AF: 0.0000188 AC: 1 AN: 53189

Other (OTH) AF: 0.00 AC: 0 AN: 1496

Alfa AF: 0.000187 Hom.: 1

ExAC AF: 0.0000412 AC: 5

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.44	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	18
DANN	Benign	0.94
DEOGEN2	Benign	0.058	T
FATHMM_MKL	Benign	0.74	D
LIST_S2	Benign	0.68	T
M_CAP	Uncertain	0.19	D
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.97	L
PhyloP100		2.0
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-0.74	N
REVEL	Benign	0.076
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.052	T
Polyphen		0.0020	B
Vest4		0.22
MutPred		0.20		Loss of loop (P = 0.0203)
MVP		0.36
MPC		0.31
ClinPred		0.15	T
GERP RS		3.3
Varity_R		0.16
gMVP		0.24
Mutation Taster		=98/2	polymorphism

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

Other links and lift over

dbSNP: rs764543196; hg19: chrX-112022359;