Variant 17-81956747-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_178493.6(NOTUM):c.891C>T(p.Tyr297=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0044 in 1,612,034 control chromosomes in the GnomAD database, including 23 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0035 ( 1 hom., cov: 33)

Exomes 𝑓: 0.0045 ( 22 hom. )

Consequence

NOTUM
NM_178493.6 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.17

Variant links:

Genes affected

NOTUM (HGNC:27106): (notum, palmitoleoyl-protein carboxylesterase) Enables palmitoleyl hydrolase activity. Involved in negative regulation of Wnt signaling pathway and protein depalmitoleylation. Acts upstream of or within bone development and regulation of bone mineralization. Predicted to be located in endoplasmic reticulum lumen and extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

NOTUM links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.53).

BP6

Variant 17-81956747-G-A is Benign according to our data. Variant chr17-81956747-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2648476.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=1.17 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 22 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NOTUM	NM_178493.6 linkuse as main transcript	c.891C>T	p.Tyr297=	synonymous_variant	8/11	ENST00000409678.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NOTUM	ENST00000409678.8 linkuse as main transcript	c.891C>T	p.Tyr297=	synonymous_variant	8/11	1	NM_178493.6	P1
NOTUM	ENST00000477214.5 linkuse as main transcript	c.465C>T	p.Tyr155=	synonymous_variant	7/8	5

Frequencies

GnomAD3 genomes

AF:

0.00352

AC:

536

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00104

Gnomad AMI

AF:

0.0504

Gnomad AMR

AF:

0.00419

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00104

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00537

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00247

AC:

609

AN:

246122

Hom.:

AF XY:

0.00247

AC XY:

331

AN XY:

134142

show subpopulations

Gnomad AFR exome

AF:

0.000780

Gnomad AMR exome

AF:

0.00256

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000663

Gnomad NFE exome

AF:

0.00433

Gnomad OTH exome

AF:

0.00268

GnomAD4 exome

AF:

0.00449

AC:

6549

AN:

1459720

Hom.:

Cov.:

AF XY:

0.00441

AC XY:

3202

AN XY:

726208

show subpopulations

Gnomad4 AFR exome

AF:

0.000478

Gnomad4 AMR exome

AF:

0.00291

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.000749

Gnomad4 NFE exome

AF:

0.00553

Gnomad4 OTH exome

AF:

0.00352

GnomAD4 genome

AF:

0.00352

AC:

536

AN:

152314

Hom.:

Cov.:

AF XY:

0.00328

AC XY:

244

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.00103

Gnomad4 AMR

AF:

0.00418

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00104

Gnomad4 NFE

AF:

0.00537

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.00345

Hom.:

Bravo

AF:

0.00354

EpiCase

AF:

0.00480

EpiControl

AF:

0.00373

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Aug 01, 2022

NOTUM: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.53

CADD

Benign

8.3

DANN

Benign

0.55

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over