GeneBe

rs1060501103

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP6

The NM_016169.4(SUFU):​c.757-11_757-7delTTTTC variant causes a splice region, intron change. The variant allele was found at a frequency of 0.00000342 in 1,461,822 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

SUFU
NM_016169.4 splice_region, intron

Scores

Not classified

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: 4.97

Publications

0 publications found
Variant links:
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

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP6
Variant 10-102597125-GTTCTT-G is Benign according to our data. Variant chr10-102597125-GTTCTT-G is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 406378.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SUFUNM_016169.4 linkc.757-11_757-7delTTTTC splice_region_variant, intron_variant Intron 6 of 11 ENST00000369902.8 NP_057253.2 Q9UMX1-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SUFUENST00000369902.8 linkc.757-14_757-10delTTCTT intron_variant Intron 6 of 11 1 NM_016169.4 ENSP00000358918.4 Q9UMX1-1
SUFUENST00000423559.2 linkc.757-14_757-10delTTCTT intron_variant Intron 6 of 9 1 ENSP00000411597.2 Q9UMX1-3
SUFUENST00000369899.6 linkc.757-14_757-10delTTCTT intron_variant Intron 6 of 10 1 ENSP00000358915.2 Q9UMX1-2
SUFUENST00000471000.1 linkn.539-14_539-10delTTCTT intron_variant Intron 4 of 5 5

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD2 exomes
AF:
0.00000398
AC:
1
AN:
251364
AF XY:
0.00000736
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.000163
GnomAD4 exome
AF:
0.00000342
AC:
5
AN:
1461822
Hom.:
0
AF XY:
0.00000413
AC XY:
3
AN XY:
727214
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33480
American (AMR)
AF:
0.0000447
AC:
2
AN:
44722
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26136
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39700
South Asian (SAS)
AF:
0.00
AC:
0
AN:
86258
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53360
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5768
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
1112008
Other (OTH)
AF:
0.0000497
AC:
3
AN:
60390
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.405
Heterozygous variant carriers
0
1
1
2
2
3
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
Cov.:
32
Alfa
AF:
0.0000712
Hom.:
0
Bravo
AF:
0.00000378

ClinVar

Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:1
Revision: criteria provided, conflicting classifications
LINK: link

Submissions by phenotype

not provided Uncertain:1
Oct 21, 2024
GeneDx
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing

In silico analysis is inconclusive as to whether the variant alters gene splicing. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown.; Not observed at significant frequency in large population cohorts (gnomAD); Has not been previously published as pathogenic or benign to our knowledge -

Gorlin syndrome;C0025149:Medulloblastoma Benign:1
Dec 18, 2024
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
PhyloP100
5.0

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs1060501103; hg19: chr10-104356882; API