10-102504050-C-A

Variant names:

• chr10-102504050-C-A
• rs886046653
• NM_016169.4:c.-103C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_016169.4(SUFU):​c.-103C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000791 in 1,263,490 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.9e-7 (0 hom.)
• Consequence: SUFU NM_016169.4 5_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.818
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.42).

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.-103C>A		5_prime_UTR	Exon 1 of 12	NP_057253.2
	SUFU	NM_001178133.2		c.-103C>A		5_prime_UTR	Exon 1 of 11	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.-103C>A		5_prime_UTR	Exon 1 of 12	ENSP00000358918.4	Q9UMX1-1
	SUFU	ENST00000369899.6	TSL:1	c.-103C>A		5_prime_UTR	Exon 1 of 11	ENSP00000358915.2	Q9UMX1-2
	SUFU	ENST00000929518.1		c.-103C>A		5_prime_UTR	Exon 1 of 13	ENSP00000599577.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.91e-7 AC: 1 AN: 1263490 Hom.: 0 Cov.: 23 AF XY: 0.00000162 AC XY: 1 AN XY: 617428

African (AFR) AF: 0.00 AC: 0 AN: 27398

American (AMR) AF: 0.00 AC: 0 AN: 22372

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19076

East Asian (EAS) AF: 0.00 AC: 0 AN: 34136

South Asian (SAS) AF: 0.00 AC: 0 AN: 64510

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 30496

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3598

European-Non Finnish (NFE) AF: 9.91e-7 AC: 1 AN: 1009156

Other (OTH) AF: 0.00 AC: 0 AN: 52748

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Medulloblastoma (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
CADD	Benign	13
DANN	Benign	0.97
PhyloP100		-0.82
PromoterAI		-0.051	Neutral

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: rs886046653; hg19: chr10-104263807;