dbSNP rs1402910700: YAP1:p.Pro19Thr (chr11-102110903-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001130145.3(YAP1):c.55C>A(p.Pro19Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000779 in 1,283,478 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P19S) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.8e-7 ( 0 hom. )

Consequence

YAP1
NM_001130145.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.240

Publications

0 publications found

Variant links:

Genes affected

YAP1 (HGNC:16262): (Yes1 associated transcriptional regulator) This gene encodes a downstream nuclear effector of the Hippo signaling pathway which is involved in development, growth, repair, and homeostasis. This gene is known to play a role in the development and progression of multiple cancers as a transcriptional regulator of this signaling pathway and may function as a potential target for cancer treatment. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Aug 2013]

YAP1 Gene-Disease associations (from GenCC):

uveal coloboma-cleft lip and palate-intellectual disability
Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia, Orphanet, G2P

YAP1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.11267179).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001130145.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
YAP1	NM_001130145.3	MANE Select	c.55C>A	p.Pro19Thr	missense	Exon 1 of 9	NP_001123617.1	P46937-1
YAP1	NM_001282101.2		c.55C>A	p.Pro19Thr	missense	Exon 1 of 9	NP_001269030.1	P46937-9
YAP1	NM_001282100.2		c.55C>A	p.Pro19Thr	missense	Exon 1 of 8	NP_001269029.1	P46937-8

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
YAP1	ENST00000282441.10	TSL:1 MANE Select	c.55C>A	p.Pro19Thr	missense	Exon 1 of 9	ENSP00000282441.5	P46937-1
YAP1	ENST00000531439.5	TSL:1	c.55C>A	p.Pro19Thr	missense	Exon 1 of 8	ENSP00000431574.1	P46937-2
YAP1	ENST00000951261.1		c.55C>A	p.Pro19Thr	missense	Exon 1 of 10	ENSP00000621320.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.79e-7

AC:

AN:

1283478

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

632362

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

25252

American (AMR)

AF:

0.00

AC:

AN:

20564

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21156

East Asian (EAS)

AF:

0.0000375

AC:

AN:

26648

South Asian (SAS)

AF:

0.00

AC:

AN:

66206

European-Finnish (FIN)

AF:

0.00

AC:

AN:

41496

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3674

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1026428

Other (OTH)

AF:

0.00

AC:

AN:

52054

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.58

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.14

Eigen

Benign

-0.56

Eigen_PC

Benign

-0.51

FATHMM_MKL

Benign

0.20

LIST_S2

Benign

0.79

M_CAP

Pathogenic

0.42

MetaRNN

Benign

0.11

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.2

PhyloP100

0.24

PrimateAI

Pathogenic

0.85

PROVEAN

Benign

-0.69

REVEL

Benign

0.056

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

0.0

Vest4

0.12

MutPred

0.26

Gain of phosphorylation at P19 (P = 0.0065)

MVP

0.043

MPC

1.3

ClinPred

0.52

GERP RS

1.9

PromoterAI

-0.042

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.0

Varity_R

0.16

gMVP

0.37

Mutation Taster

=91/9

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over