chr10-102504174-G-A

Position:

• chr10-102504174-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_016169.4(SUFU):​c.22G>A​(p.Gly8Ser) 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. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: SUFU NM_016169.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.977

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_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.021559179).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SUFU	NM_016169.4	c.22G>A	p.Gly8Ser	missense_variant	1/12	ENST00000369902.8	NP_057253.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SUFU	ENST00000369902.8	c.22G>A	p.Gly8Ser	missense_variant	1/12	1	NM_016169.4	ENSP00000358918.4
SUFU	ENST00000423559.2	c.22G>A	p.Gly8Ser	missense_variant	1/10	1		ENSP00000411597.2
SUFU	ENST00000369899.6	c.22G>A	p.Gly8Ser	missense_variant	1/11	1		ENSP00000358915.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ExAC AF: 0.0000109 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.099
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.13	T;.;.
Eigen	Benign	-0.40
Eigen_PC	Benign	-0.24
FATHMM_MKL	Benign	0.66	D
LIST_S2	Uncertain	0.89	D;D;D
M_CAP	Pathogenic	0.30	D
MetaRNN	Benign	0.022	T;T;T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	0.69	N;N;N
PrimateAI	Pathogenic	0.84	D
PROVEAN	Benign	0.48	N;N;N
REVEL	Benign	0.047
Sift	Benign	0.52	T;T;T
Sift4G	Benign	0.62	T;T;T
Polyphen		0.0060	B;B;B
Vest4		0.15
MutPred		0.16		Gain of glycosylation at G8 (P = 4e-04);Gain of glycosylation at G8 (P = 4e-04);Gain of glycosylation at G8 (P = 4e-04);
MVP		0.48
MPC		0.62
ClinPred		0.40	T
GERP RS		3.3
Varity_R		0.14
gMVP		0.26

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: rs769696737; hg19: chr10-104263931;