10-102548689-C-T

Variant names:

• chr10-102548689-C-T
• rs10883735
• NM_016169.4:c.318-1281C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016169.4(SUFU):​c.318-1281C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.101 in 152,174 control chromosomes in the GnomAD database, including 1,247 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.10 (1247 hom., cov: 32)
• Consequence: SUFU NM_016169.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.429
• Publications: 10 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.4 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.318-1281C>T		intron	N/A	NP_057253.2
	SUFU	NM_001178133.2		c.318-1281C>T		intron	N/A	NP_001171604.1	Q9UMX1-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SUFU	ENST00000369902.8	TSL:1 MANE Select	c.318-1281C>T		intron	N/A	ENSP00000358918.4	Q9UMX1-1
	SUFU	ENST00000423559.2	TSL:1	c.318-1281C>T		intron	N/A	ENSP00000411597.2	Q9UMX1-3
	SUFU	ENST00000369899.6	TSL:1	c.318-1281C>T		intron	N/A	ENSP00000358915.2	Q9UMX1-2

Frequencies

GnomAD3 genomes AF: 0.101 AC: 15329 AN: 152054 Hom.: 1243 Cov.: 32

Gnomad AFR AF: 0.0432

Gnomad AMI AF: 0.124

Gnomad AMR AF: 0.177

Gnomad ASJ AF: 0.0626

Gnomad EAS AF: 0.415

Gnomad SAS AF: 0.221

Gnomad FIN AF: 0.0713

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0920

Gnomad OTH AF: 0.122

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.101 AC: 15356 AN: 152174 Hom.: 1247 Cov.: 32 AF XY: 0.106 AC XY: 7854 AN XY: 74400

African (AFR) AF: 0.0432 AC: 1793 AN: 41524

American (AMR) AF: 0.178 AC: 2722 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0626 AC: 217 AN: 3466

East Asian (EAS) AF: 0.415 AC: 2141 AN: 5162

South Asian (SAS) AF: 0.222 AC: 1072 AN: 4818

European-Finnish (FIN) AF: 0.0713 AC: 755 AN: 10596

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.0920 AC: 6258 AN: 67998

Other (OTH) AF: 0.126 AC: 266 AN: 2114

Alfa AF: 0.0434 Hom.: 45

Bravo AF: 0.108

Asia WGS AF: 0.301 AC: 1042 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.4
DANN	Benign	0.37
PhyloP100		-0.43
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: rs10883735; hg19: chr10-104308446;