rs1554852823

Variant names:

• chr10-102597285-C-A
• NM_016169.4:c.902C>A

Your query was ambiguous. Multiple possible variants found:

• chr10-102597285-C-A
• chr10-102597285-C-G
• chr10-102597285-C-T

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM1 PM2 PP3_Moderate

The NM_016169.4(SUFU):​c.902C>A​(p.Ser301Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SUFU NM_016169.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.57

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]

ACMG classification

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

• PM1: In a modified_residue Phosphoserine (size 0) in uniprot entity SUFU_HUMAN
• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.856

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SUFU	NM_016169.4	c.902C>A	p.Ser301Tyr	missense_variant	Exon 7 of 12	ENST00000369902.8	NP_057253.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SUFU	ENST00000369902.8	c.902C>A	p.Ser301Tyr	missense_variant	Exon 7 of 12	1	NM_016169.4	ENSP00000358918.4
SUFU	ENST00000423559.2	c.902C>A	p.Ser301Tyr	missense_variant	Exon 7 of 10	1		ENSP00000411597.2
SUFU	ENST00000369899.6	c.902C>A	p.Ser301Tyr	missense_variant	Exon 7 of 11	1		ENSP00000358915.2
SUFU	ENST00000471000.1	n.684C>A		non_coding_transcript_exon_variant	Exon 5 of 6	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.79
BayesDel_addAF	Pathogenic	0.31	D
BayesDel_noAF	Pathogenic	0.21
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.44	T;.;.
Eigen	Pathogenic	0.88
Eigen_PC	Pathogenic	0.88
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Pathogenic	0.99	D;D;D
M_CAP	Uncertain	0.17	D
MetaRNN	Pathogenic	0.86	D;D;D
MetaSVM	Uncertain	0.026	D
MutationAssessor	Benign	1.7	L;L;L
PrimateAI	Pathogenic	0.83	D
PROVEAN	Uncertain	-2.7	D;D;D
REVEL	Uncertain	0.62
Sift	Uncertain	0.0030	D;D;D
Sift4G	Uncertain	0.016	D;D;D
Polyphen		1.0	D;D;D
Vest4		0.86
MutPred		0.54		Loss of phosphorylation at S301 (P = 0.0112);Loss of phosphorylation at S301 (P = 0.0112);Loss of phosphorylation at S301 (P = 0.0112);
MVP		0.65
MPC		1.7
ClinPred		0.99	D
GERP RS		6.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.42
gMVP		0.73

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-104357042;