dbSNP rs200123694: AMOT:p.Pro982Pro (chrX-112779208-C-T) – ACMG Classification: Benign (-15 pts)

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_001113490.2(AMOT):c.2946G>A(p.Pro982Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000891 in 739,329 control chromosomes in the GnomAD database, including 8 homozygotes. There are 210 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0010 ( 5 hom., 32 hem., cov: 23)

Exomes 𝑓: 0.00087 ( 3 hom. 178 hem. )

Consequence

AMOT
NM_001113490.2 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.39

Publications

1 publications found

Variant links:

COSMIC-nc: COSV59061441

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]

AMOT links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant X-112779208-C-T is Benign according to our data. Variant chrX-112779208-C-T is described in ClinVar as Benign. ClinVar VariationId is 734333.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-2.39 with no splicing effect.

BS1

Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.00104 (116/111720) while in subpopulation EAS AF = 0.0219 (78/3559). AF 95% confidence interval is 0.018. There are 5 homozygotes in GnomAd4. There are 32 alleles in the male GnomAd4 subpopulation. Median coverage is 23. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 5 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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
AMOT	NM_001113490.2	MANE Select	c.2946G>A	p.Pro982Pro	synonymous	Exon 13 of 14	NP_001106962.1	Q4VCS5-1
AMOT	NM_001386998.1		c.2946G>A	p.Pro982Pro	synonymous	Exon 14 of 15	NP_001373927.1	Q4VCS5-1
AMOT	NM_001386999.1		c.2946G>A	p.Pro982Pro	synonymous	Exon 13 of 14	NP_001373928.1	Q4VCS5-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
AMOT	ENST00000371959.9	TSL:1 MANE Select	c.2946G>A	p.Pro982Pro	synonymous	Exon 13 of 14	ENSP00000361027.3	Q4VCS5-1
AMOT	ENST00000371962.5	TSL:1	c.2250G>A	p.Pro750Pro	synonymous	Exon 10 of 11	ENSP00000361030.1	E7ERM3
AMOT	ENST00000304758.5	TSL:1	c.1719G>A	p.Pro573Pro	synonymous	Exon 11 of 12	ENSP00000305557.1	Q4VCS5-2

Frequencies

GnomAD3 genomes

AF:

0.00105

AC:

117

AN:

111667

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00875

Gnomad AMR

AF:

0.00257

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0221

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000188

Gnomad OTH

AF:

0.00269

GnomAD2 exomes

AF:

0.00163

AC:

279

AN:

171198

AF XY:

0.00158

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0208

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000406

Gnomad OTH exome

AF:

0.000230

GnomAD4 exome

AF:

0.000865

AC:

543

AN:

627609

Hom.:

Cov.:

AF XY:

0.000945

AC XY:

178

AN XY:

188379

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

17283

American (AMR)

AF:

0.0000294

AC:

AN:

34038

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

16394

East Asian (EAS)

AF:

0.0155

AC:

434

AN:

27965

South Asian (SAS)

AF:

0.000245

AC:

AN:

44811

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40135

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3076

European-Non Finnish (NFE)

AF:

0.0000460

AC:

AN:

413358

Other (OTH)

AF:

0.00255

AC:

AN:

30549

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

121

151

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00104

AC:

116

AN:

111720

Hom.:

Cov.:

AF XY:

0.000943

AC XY:

AN XY:

33936

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30751

American (AMR)

AF:

0.00257

AC:

AN:

10507

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2643

East Asian (EAS)

AF:

0.0219

AC:

AN:

3559

South Asian (SAS)

AF:

0.00

AC:

AN:

2633

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6068

Middle Eastern (MID)

AF:

0.00

AC:

AN:

219

European-Non Finnish (NFE)

AF:

0.0000188

AC:

AN:

53149

Other (OTH)

AF:

0.00266

AC:

AN:

1505

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000285

Hom.:

Bravo

AF:

0.000933

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.42

(source)

DANN

Benign

0.58

PhyloP100

-2.4

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over