NM_016169.4:c.*1122C>T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 21 publications found

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 Gene-Disease associations (from GenCC):

• medulloblastoma

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: ClinGen, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• nevoid basal cell carcinoma syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Illumina, Genomics England PanelApp, Orphanet
• basal cell nevus syndrome 2

  Inheritance: AD Classification: STRONG Submitted by: G2P
• neurodevelopmental disorder

  Inheritance: AD Classification: STRONG Submitted by: PanelApp Australia
• ocular motor apraxia, Cogan type

  Inheritance: AD Classification: STRONG Submitted by: Franklin by Genoox
• Joubert syndrome 32

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: G2P, PanelApp Australia, Labcorp Genetics (formerly Invitae), Ambry Genetics
• Joubert syndrome

  Inheritance: AD, AR Classification: MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet
• apraxia

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
• ciliopathy

  Inheritance: AR Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016169.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SUFU	NM_016169.4	MANE Select	c.*1122C>T		3_prime_UTR	Exon 12 of 12	NP_057253.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SUFU	ENST00000369902.8	TSL:1 MANE Select	c.*1122C>T		3_prime_UTR	Exon 12 of 12	ENSP00000358918.4	Q9UMX1-1
	SUFU	ENST00000929518.1		c.*1122C>T		3_prime_UTR	Exon 13 of 13	ENSP00000599577.1
	SUFU	ENST00000893176.1		c.*1122C>T		3_prime_UTR	Exon 13 of 13	ENSP00000563235.1

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

African (AFR) AF: 0.155 AC: 605 AN: 3906

American (AMR) AF: 0.178 AC: 445 AN: 2502

Ashkenazi Jewish (ASJ) AF: 0.328 AC: 1681 AN: 5128

East Asian (EAS) AF: 0.124 AC: 1410 AN: 11414

South Asian (SAS) AF: 0.201 AC: 143 AN: 710

European-Finnish (FIN) AF: 0.300 AC: 36 AN: 120

Middle Eastern (MID) AF: 0.200 AC: 99 AN: 496

European-Non Finnish (NFE) AF: 0.292 AC: 14648 AN: 50126

Other (OTH) AF: 0.268 AC: 1825 AN: 6800

GnomAD4 genome AF: 0.236 AC: 35960 AN: 152072 Hom.: 4633 Cov.: 32 AF XY: 0.234 AC XY: 17406 AN XY: 74344

African (AFR) AF: 0.150 AC: 6215 AN: 41472

American (AMR) AF: 0.202 AC: 3084 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.317 AC: 1097 AN: 3466

East Asian (EAS) AF: 0.142 AC: 736 AN: 5170

South Asian (SAS) AF: 0.222 AC: 1070 AN: 4814

European-Finnish (FIN) AF: 0.281 AC: 2971 AN: 10570

Middle Eastern (MID) AF: 0.279 AC: 82 AN: 294

European-Non Finnish (NFE) AF: 0.291 AC: 19802 AN: 67974

Other (OTH) AF: 0.259 AC: 546 AN: 2110

Alfa AF: 0.263 Hom.: 12030

Bravo AF: 0.225

Asia WGS AF: 0.178 AC: 622 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Medulloblastoma (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	8.0
DANN	Benign	0.71
PhyloP100		0.24
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11596235; hg19: chr10-104391034;