Variant 10-102504350-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_016169.4(SUFU):c.182+16C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.515 in 1,613,042 control chromosomes in the GnomAD database, including 219,966 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.46 ( 17119 hom., cov: 32)

Exomes 𝑓: 0.52 ( 202847 hom. )

Consequence

SUFU
NM_016169.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:11

Conservation

PhyloP100: -0.175

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 -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.42).

BP6

Variant 10-102504350-C-T is Benign according to our data. Variant chr10-102504350-C-T is described in ClinVar as [Benign]. Clinvar id is 260689.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-102504350-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.542 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SUFU	NM_016169.4 link	c.182+16C>T		intron_variant		ENST00000369902.8	NP_057253.2	Q9UMX1-1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
SUFU	ENST00000369902.8 link	c.182+16C>T	intron_variant	1	NM_016169.4	ENSP00000358918.4	Q9UMX1-1
SUFU	ENST00000423559.2 link	c.182+16C>T	intron_variant	1		ENSP00000411597.2	Q9UMX1-3
SUFU	ENST00000369899.6 link	c.182+16C>T	intron_variant	1		ENSP00000358915.2	Q9UMX1-2

Frequencies

GnomAD3 genomes

AF:

0.461

AC:

70016

AN:

151774

Hom.:

17115

Cov.:

show subpopulations

Gnomad AFR

AF:

0.318

Gnomad AMI

AF:

0.415

Gnomad AMR

AF:

0.412

Gnomad ASJ

AF:

0.676

Gnomad EAS

AF:

0.321

Gnomad SAS

AF:

0.488

Gnomad FIN

AF:

0.521

Gnomad MID

AF:

0.620

Gnomad NFE

AF:

0.547

Gnomad OTH

AF:

0.500

GnomAD3 exomes

AF:

0.476

AC:

117166

AN:

246288

Hom.:

29598

AF XY:

0.489

AC XY:

65523

AN XY:

133900

show subpopulations

Gnomad AFR exome

AF:

0.313

Gnomad AMR exome

AF:

0.299

Gnomad ASJ exome

AF:

0.662

Gnomad EAS exome

AF:

0.322

Gnomad SAS exome

AF:

0.489

Gnomad FIN exome

AF:

0.520

Gnomad NFE exome

AF:

0.548

Gnomad OTH exome

AF:

0.526

GnomAD4 exome

AF:

0.521

AC:

761462

AN:

1461150

Hom.:

202847

Cov.:

AF XY:

0.523

AC XY:

379841

AN XY:

726814

show subpopulations

Gnomad4 AFR exome

AF:

0.310

Gnomad4 AMR exome

AF:

0.313

Gnomad4 ASJ exome

AF:

0.665

Gnomad4 EAS exome

AF:

0.267

Gnomad4 SAS exome

AF:

0.486

Gnomad4 FIN exome

AF:

0.523

Gnomad4 NFE exome

AF:

0.544

Gnomad4 OTH exome

AF:

0.525

GnomAD4 genome

AF:

0.461

AC:

70038

AN:

151892

Hom.:

17119

Cov.:

AF XY:

0.458

AC XY:

33956

AN XY:

74214

show subpopulations

Gnomad4 AFR

AF:

0.318

Gnomad4 AMR

AF:

0.411

Gnomad4 ASJ

AF:

0.676

Gnomad4 EAS

AF:

0.321

Gnomad4 SAS

AF:

0.487

Gnomad4 FIN

AF:

0.521

Gnomad4 NFE

AF:

0.547

Gnomad4 OTH

AF:

0.500

Alfa

AF:

0.533

Hom.:

36338

Bravo

AF:

0.442

Asia WGS

AF:

0.385

AC:

1341

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:11

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	May 25, 2016	Variant summary: The SUFU c.182+16C>T variant involves the alteration of a non-conserved intronic nucleotide at a position not widely known to affect splicing. 4/5 splice prediction tools predict no significant impact on normal splicing. This variant was found in 57271/117778 control chromosomes (including 14438 homozygotes) at a frequency of 0.4862623, which is approximately 482372 times the estimated maximal expected allele frequency of a pathogenic SUFU variant (0.000001), suggesting this variant is a common benign polymorphism. Therefore based on the nature and position of this variant and a high allele frequency in general population, it is classified as Benign. -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -

Joubert syndrome 32

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 15, 2021

- -

Gorlin syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 15, 2021

- -

Gorlin syndrome;C0025149:Medulloblastoma

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Familial meningioma

Benign:1

Benign, criteria provided, single submitter

clinical testing

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Jul 07, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Benign

0.97

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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