chr11-102111084-A-T

Variant names:

• chr11-102111084-A-T
• rs965501205
• NM_001130145.3:c.236A>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001130145.3(YAP1):​c.236A>T​(p.Asn79Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,148 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: YAP1 NM_001130145.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.27

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20700437).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
YAP1	NM_001130145.3	c.236A>T	p.Asn79Ile	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.236A>T	p.Asn79Ile	missense_variant	Exon 1 of 9	1	NM_001130145.3	ENSP00000282441.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461148 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 726906

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000282 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	22
DANN	Benign	0.92
DEOGEN2	Uncertain	0.57	.;D;.;.;.;.;.
Eigen	Benign	-0.41
Eigen_PC	Benign	-0.34
FATHMM_MKL	Benign	0.28	N
LIST_S2	Benign	0.85	T;T;T;T;T;T;T
M_CAP	Pathogenic	0.68	D
MetaRNN	Benign	0.21	T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L;L;L;L;L;L;L
PrimateAI	Pathogenic	0.90	D
PROVEAN	Uncertain	-2.8	D;D;D;D;.;.;D
REVEL	Benign	0.041
Sift	Benign	0.15	T;T;T;T;.;.;T
Sift4G	Benign	0.21	T;T;T;T;T;T;T
Polyphen		0.47, 0.0040, 0.0010	.;P;.;.;.;B;B
Vest4		0.22
MutPred		0.39		Loss of disorder (P = 0.0269);Loss of disorder (P = 0.0269);Loss of disorder (P = 0.0269);Loss of disorder (P = 0.0269);Loss of disorder (P = 0.0269);Loss of disorder (P = 0.0269);Loss of disorder (P = 0.0269);
MVP		0.068
MPC		1.5
ClinPred		0.19	T
GERP RS		2.7
Varity_R		0.57
gMVP		0.20

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: rs965501205; hg19: chr11-101981815;