rs11596235

Variant names:

• chr10-102631277-C-T
• rs11596235
• NM_016169.4:c.*1122C>T

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.*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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.241

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=-0.77).
• 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 rank	MANE	Protein	UniProt
SUFU	NM_016169.4	c.*1122C>T		3_prime_UTR_variant	Exon 12 of 12	ENST00000369902.8	NP_057253.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SUFU	ENST00000369902.8	c.*1122C>T		3_prime_UTR_variant	Exon 12 of 12	1	NM_016169.4	ENSP00000358918.4

Frequencies

GnomAD3 genomes AF: 0.236 AC: 35933 AN: 151954 Hom.: 4630 Cov.: 32

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.: 0 AF XY: 0.260 AC XY: 9704 AN XY: 37348

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.: 32 AF XY: 0.234 AC XY: 17406 AN XY: 74344

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

Submissions by phenotype

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Medulloblastoma Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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

Other links and lift over

dbSNP: rs11596235; hg19: chr10-104391034;