rs12414407

Positions:

• chr10-102627262-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_016169.4(SUFU):​c.1365+19T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.654 in 1,609,952 control chromosomes in the GnomAD database, including 346,385 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.68 (35758 hom., cov: 34)
  • Exomes 𝑓: 0.65 (310627 hom.)
• Consequence: SUFU NM_016169.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:11
• Conservation: PhyloP100: 0.452

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 10-102627262-T-C is Benign according to our data. Variant chr10-102627262-T-C is described in ClinVar as [Benign]. Clinvar id is 260688.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-102627262-T-C is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.745 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SUFU	NM_016169.4	c.1365+19T>C		intron_variant		ENST00000369902.8	NP_057253.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SUFU	ENST00000369902.8	c.1365+19T>C		intron_variant		1	NM_016169.4	ENSP00000358918.4

Frequencies

GnomAD3 genomes AF: 0.683 AC: 103853 AN: 152102 Hom.: 35723 Cov.: 34

Gnomad AFR AF: 0.752

Gnomad AMI AF: 0.599

Gnomad AMR AF: 0.634

Gnomad ASJ AF: 0.701

Gnomad EAS AF: 0.748

Gnomad SAS AF: 0.711

Gnomad FIN AF: 0.607

Gnomad MID AF: 0.706

Gnomad NFE AF: 0.656

Gnomad OTH AF: 0.702

GnomAD3 exomes AF: 0.659 AC: 165628 AN: 251454 Hom.: 55054 AF XY: 0.662 AC XY: 89918 AN XY: 135898

Gnomad AFR exome AF: 0.754

Gnomad AMR exome AF: 0.578

Gnomad ASJ exome AF: 0.689

Gnomad EAS exome AF: 0.745

Gnomad SAS exome AF: 0.714

Gnomad FIN exome AF: 0.609

Gnomad NFE exome AF: 0.647

Gnomad OTH exome AF: 0.659

GnomAD4 exome AF: 0.651 AC: 949428 AN: 1457730 Hom.: 310627 Cov.: 33 AF XY: 0.654 AC XY: 474177 AN XY: 725372

Gnomad4 AFR exome AF: 0.760

Gnomad4 AMR exome AF: 0.587

Gnomad4 ASJ exome AF: 0.689

Gnomad4 EAS exome AF: 0.720

Gnomad4 SAS exome AF: 0.712

Gnomad4 FIN exome AF: 0.613

Gnomad4 NFE exome AF: 0.643

Gnomad4 OTH exome AF: 0.670

GnomAD4 genome AF: 0.683 AC: 103944 AN: 152222 Hom.: 35758 Cov.: 34 AF XY: 0.680 AC XY: 50603 AN XY: 74434

Gnomad4 AFR AF: 0.752

Gnomad4 AMR AF: 0.633

Gnomad4 ASJ AF: 0.701

Gnomad4 EAS AF: 0.747

Gnomad4 SAS AF: 0.711

Gnomad4 FIN AF: 0.607

Gnomad4 NFE AF: 0.656

Gnomad4 OTH AF: 0.705

Alfa AF: 0.659 Hom.: 18444

Bravo AF: 0.685

Asia WGS AF: 0.716 AC: 2487 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:11

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:4

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, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
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	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	clinical testing	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	May 26, 2016	Variant summary: The SUFU c.1365+19T>C variant involves the alteration of a non-conserved intronic nucleotide. Mutation taster predicts the variant to be neutral along with 5/5 splice prediction tools predict no significant impact on normal splicing. This variant was found in 80437/121368 control chromosomes (including 26892 homozygotes) at a frequency of 0.6627529, indicating the variant to be the ancestral allele and a common benign polymorphism. Taken together, this variant is classified as Benign. -

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	-0.80
CADD	Benign	7.0
DANN	Benign	0.60

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: rs12414407; hg19: chr10-104387019; COSMIC: COSV64017850;