10-102594059-C-G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_016169.4(SUFU):​c.750C>G​(p.His250Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H250R) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

SUFU
NM_016169.4 missense

Scores

5
14

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.111

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

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ACMG classification

Classification was made for transcript

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 (MetaRNN=0.15326959).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SUFUNM_016169.4 linkc.750C>G p.His250Gln missense_variant Exon 6 of 12 ENST00000369902.8 NP_057253.2 Q9UMX1-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SUFUENST00000369902.8 linkc.750C>G p.His250Gln missense_variant Exon 6 of 12 1 NM_016169.4 ENSP00000358918.4 Q9UMX1-1
SUFUENST00000423559.2 linkc.750C>G p.His250Gln missense_variant Exon 6 of 10 1 ENSP00000411597.2 Q9UMX1-3
SUFUENST00000369899.6 linkc.750C>G p.His250Gln missense_variant Exon 6 of 11 1 ENSP00000358915.2 Q9UMX1-2
SUFUENST00000471000.1 linkn.532C>G non_coding_transcript_exon_variant Exon 4 of 6 5

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.16
BayesDel_addAF
Uncertain
0.12
D
BayesDel_noAF
Uncertain
-0.070
CADD
Benign
20
DANN
Benign
0.96
DEOGEN2
Benign
0.14
T;.;.
Eigen
Benign
-0.45
Eigen_PC
Benign
-0.29
FATHMM_MKL
Uncertain
0.83
D
LIST_S2
Benign
0.74
T;T;T
M_CAP
Benign
0.032
D
MetaRNN
Benign
0.15
T;T;T
MetaSVM
Benign
-0.80
T
MutationAssessor
Benign
-0.69
N;N;N
PhyloP100
0.11
PrimateAI
Uncertain
0.71
T
PROVEAN
Benign
-0.33
N;N;N
REVEL
Uncertain
0.41
Sift
Benign
0.34
T;T;T
Sift4G
Benign
0.53
T;T;T
Polyphen
0.0
B;B;B
Vest4
0.20
MutPred
0.34
Gain of disorder (P = 0.1621);Gain of disorder (P = 0.1621);Gain of disorder (P = 0.1621);
MVP
0.92
MPC
0.61
ClinPred
0.31
T
GERP RS
1.5
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.41
gMVP
0.50
Mutation Taster
=31/69
disease causing

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.030
Details are displayed if max score is > 0.2

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

Publications

Other links and lift over

dbSNP: rs1235137905; hg19: chr10-104353816; API