rs34135067

chr10-102599540-G-Cchr10-102599540-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2 PP2 BP4_Moderate

The NM_016169.4(SUFU):c.1018G>C(p.Ala340Pro) 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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A340S) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SUFU NM_016169.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.71

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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant where missense usually causes diseases, SUFU
• BP4: Computational evidence support a benign effect (MetaRNN=0.11249557).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SUFU	NM_016169.4	c.1018G>C	p.Ala340Pro	missense_variant	8/12	ENST00000369902.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SUFU	ENST00000369902.8	c.1018G>C	p.Ala340Pro	missense_variant	8/12	1	NM_016169.4	P1
SUFU	ENST00000423559.2	c.1018G>C	p.Ala340Pro	missense_variant	8/10	1
SUFU	ENST00000369899.6	c.1018G>C	p.Ala340Pro	missense_variant	8/11	1
SUFU	ENST00000471000.1	n.800G>C		non_coding_transcript_exon_variant	6/6	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.062
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
Cadd	Benign	16
Dann	Uncertain	0.98
DEOGEN2	Benign	0.22	T;.;.
Eigen	Benign	-0.64
Eigen_PC	Benign	-0.37
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.80	T;T;T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.11	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-1.2	N;N;N
MutationTaster	Benign	0.99	D;D;D
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-0.40	N;N;N
REVEL	Benign	0.039
Sift	Benign	0.33	T;T;T
Sift4G	Benign	0.30	T;T;T
Polyphen		0.0030	B;B;B
Vest4		0.29
MutPred		0.39		Gain of glycosylation at A340 (P = 0.0213);Gain of glycosylation at A340 (P = 0.0213);Gain of glycosylation at A340 (P = 0.0213);
MVP		0.20
MPC		0.79
ClinPred		0.36	T
GERP RS		3.3
Varity_R		0.053
gMVP		0.37

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

LitVar

Other links and lift over

dbSNP: rs34135067; hg19: chr10-104359297;