Variant chr10-102631277-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_016169.4(SUFU):c.*1122C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.244 in 233,274 control chromosomes in the GnomAD database, including 7,530 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.24 ( 4633 hom., cov: 32)

Exomes 𝑓: 0.26 ( 2897 hom. )

Consequence

SUFU
NM_016169.4 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.241

Variant links:

Genes affected

SUFU (HGNC:16466): (SUFU negative regulator of hedgehog signaling) The Hedgehog signaling pathway plays an important role in early human development. The pathway is a signaling cascade that plays a role in pattern formation and cellular proliferation during development. This gene encodes a negative regulator of the hedgehog signaling pathway. Defects in this gene are a cause of medulloblastoma. Alternative splicing results in multiple transcript variants.[provided by RefSeq, May 2010]

SUFU links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BP6

Variant 10-102631277-C-T is Benign according to our data. Variant chr10-102631277-C-T is described in ClinVar as [Benign]. Clinvar id is 298587.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.288 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SUFU	NM_016169.4 linkuse as main transcript	c.*1122C>T		3_prime_UTR_variant	12/12	ENST00000369902.8	NP_057253.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SUFU	ENST00000369902.8 linkuse as main transcript	c.*1122C>T		3_prime_UTR_variant	12/12	1	NM_016169.4	ENSP00000358918	P1	Q9UMX1-1

Frequencies

GnomAD3 genomes

AF:

0.236

AC:

35933

AN:

151954

Hom.:

4630

Cov.:

show subpopulations

Gnomad AFR

AF:

0.150

Gnomad AMI

AF:

0.392

Gnomad AMR

AF:

0.202

Gnomad ASJ

AF:

0.317

Gnomad EAS

AF:

0.142

Gnomad SAS

AF:

0.220

Gnomad FIN

AF:

0.281

Gnomad MID

AF:

0.288

Gnomad NFE

AF:

0.291

Gnomad OTH

AF:

0.257

GnomAD4 exome

AF:

0.257

AC:

20892

AN:

81202

Hom.:

2897

Cov.:

AF XY:

0.260

AC XY:

9704

AN XY:

37348

show subpopulations

Gnomad4 AFR exome

AF:

0.155

Gnomad4 AMR exome

AF:

0.178

Gnomad4 ASJ exome

AF:

0.328

Gnomad4 EAS exome

AF:

0.124

Gnomad4 SAS exome

AF:

0.201

Gnomad4 FIN exome

AF:

0.300

Gnomad4 NFE exome

AF:

0.292

Gnomad4 OTH exome

AF:

0.268

GnomAD4 genome

AF:

0.236

AC:

35960

AN:

152072

Hom.:

4633

Cov.:

AF XY:

0.234

AC XY:

17406

AN XY:

74344

show subpopulations

Gnomad4 AFR

AF:

0.150

Gnomad4 AMR

AF:

0.202

Gnomad4 ASJ

AF:

0.317

Gnomad4 EAS

AF:

0.142

Gnomad4 SAS

AF:

0.222

Gnomad4 FIN

AF:

0.281

Gnomad4 NFE

AF:

0.291

Gnomad4 OTH

AF:

0.259

Alfa

AF:

0.278

Hom.:

8154

Bravo

AF:

0.225

Asia WGS

AF:

0.178

AC:

622

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Medulloblastoma

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

8.0

DANN

Benign

0.71

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