rs11594179

Variant names:

• chr10-102632823-C-T
• rs11594179
• NM_016169.4:c.*2668C>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.*2668C>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 0.178 in 233,262 control chromosomes in the GnomAD database, including 4,342 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.17 (2603 hom., cov: 32)
  • Exomes 𝑓: 0.19 (1739 hom.)
• Consequence: SUFU NM_016169.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.100
• Publications: 25 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: Ambry Genetics, Labcorp Genetics (formerly Invitae), ClinGen
• nevoid basal cell carcinoma syndrome

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

  Inheritance: AD Classification: STRONG Submitted by: G2P
• ocular motor apraxia, Cogan type

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

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

  Inheritance: AR, AD Classification: MODERATE, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics
• 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=-0.83).
• BP6: Variant 10-102632823-C-T is Benign according to our data. Variant chr10-102632823-C-T is described in ClinVar as Benign. ClinVar VariationId is 298607.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.218 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.*2668C>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.*2668C>T		3_prime_UTR	Exon 12 of 12	ENSP00000358918.4
	SUFU	ENST00000929518.1		c.*2668C>T		3_prime_UTR	Exon 13 of 13	ENSP00000599577.1
	SUFU	ENST00000893176.1		c.*2668C>T		3_prime_UTR	Exon 13 of 13	ENSP00000563235.1

Frequencies

GnomAD3 genomes AF: 0.171 AC: 25952 AN: 152036 Hom.: 2603 Cov.: 32

Gnomad AFR AF: 0.0928

Gnomad AMI AF: 0.315

Gnomad AMR AF: 0.164

Gnomad ASJ AF: 0.298

Gnomad EAS AF: 0.0470

Gnomad SAS AF: 0.140

Gnomad FIN AF: 0.175

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.221

Gnomad OTH AF: 0.204

GnomAD4 exome AF: 0.192 AC: 15536 AN: 81108 Hom.: 1739 Cov.: 0 AF XY: 0.194 AC XY: 7233 AN XY: 37328

African (AFR) AF: 0.0951 AC: 371 AN: 3902

American (AMR) AF: 0.148 AC: 371 AN: 2500

Ashkenazi Jewish (ASJ) AF: 0.309 AC: 1582 AN: 5124

East Asian (EAS) AF: 0.0248 AC: 283 AN: 11414

South Asian (SAS) AF: 0.126 AC: 88 AN: 700

European-Finnish (FIN) AF: 0.221 AC: 15 AN: 68

Middle Eastern (MID) AF: 0.175 AC: 86 AN: 492

European-Non Finnish (NFE) AF: 0.226 AC: 11314 AN: 50130

Other (OTH) AF: 0.210 AC: 1426 AN: 6778

GnomAD4 genome AF: 0.171 AC: 25953 AN: 152154 Hom.: 2603 Cov.: 32 AF XY: 0.166 AC XY: 12320 AN XY: 74384

African (AFR) AF: 0.0926 AC: 3844 AN: 41518

American (AMR) AF: 0.164 AC: 2500 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.298 AC: 1033 AN: 3466

East Asian (EAS) AF: 0.0471 AC: 244 AN: 5178

South Asian (SAS) AF: 0.140 AC: 678 AN: 4828

European-Finnish (FIN) AF: 0.175 AC: 1849 AN: 10564

Middle Eastern (MID) AF: 0.241 AC: 71 AN: 294

European-Non Finnish (NFE) AF: 0.221 AC: 15014 AN: 67996

Other (OTH) AF: 0.205 AC: 433 AN: 2114

Alfa AF: 0.209 Hom.: 6040

Bravo AF: 0.167

Asia WGS AF: 0.0920 AC: 322 AN: 3478

ClinVar

ClinVar submissions as Germline

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	-0.83
CADD	Benign	2.9
DANN	Benign	0.49
PhyloP100		0.10
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: rs11594179; hg19: chr10-104392580;