11-102110859-G-C

Variant names:

• chr11-102110859-G-C
• rs867829919
• NM_001130145.3:c.11G>C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001130145.3(YAP1):​c.11G>C​(p.Gly4Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000793 in 1,261,776 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.9e-7 (0 hom.)
• Consequence: YAP1 NM_001130145.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.249

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.043026358).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
YAP1	NM_001130145.3	c.11G>C	p.Gly4Ala	missense_variant	Exon 1 of 9	ENST00000282441.10	NP_001123617.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
YAP1	ENST00000282441.10	c.11G>C	p.Gly4Ala	missense_variant	Exon 1 of 9	1	NM_001130145.3	ENSP00000282441.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.93e-7 AC: 1 AN: 1261776 Hom.: 0 Cov.: 31 AF XY: 0.00000161 AC XY: 1 AN XY: 621494

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000196

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 10, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.11G>C (p.G4A) alteration is located in exon 1 (coding exon 1) of the YAP1 gene. This alteration results from a G to C substitution at nucleotide position 11, causing the glycine (G) at amino acid position 4 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	17
DANN	Uncertain	0.98
DEOGEN2	Benign	0.14	.;T;.;.;.;.;.
Eigen	Benign	-0.88
Eigen_PC	Benign	-0.78
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.82	T;T;T;T;T;T;T
M_CAP	Uncertain	0.17	D
MetaRNN	Benign	0.043	T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.0	L;L;L;L;L;L;L
PrimateAI	Pathogenic	0.81	D
PROVEAN	Benign	-0.66	N;N;N;N;.;.;N
REVEL	Benign	0.076
Sift	Pathogenic	0.0	D;D;D;D;.;.;D
Sift4G	Benign	0.58	T;T;T;T;T;T;T
Polyphen		0.0	.;B;.;.;.;B;B
Vest4		0.055
MutPred		0.17		Gain of glycosylation at P7 (P = 0.1525);Gain of glycosylation at P7 (P = 0.1525);Gain of glycosylation at P7 (P = 0.1525);Gain of glycosylation at P7 (P = 0.1525);Gain of glycosylation at P7 (P = 0.1525);Gain of glycosylation at P7 (P = 0.1525);Gain of glycosylation at P7 (P = 0.1525);
MVP		0.068
MPC		1.3
ClinPred		0.15	T
GERP RS		-0.10
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.3
Varity_R		0.16
gMVP		0.15

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: rs867829919; hg19: chr11-101981590;