chr10-102615290-A-T

Variant names:

• chr10-102615290-A-T
• NM_016169.4:c.1045A>T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_016169.4(SUFU):​c.1045A>T​(p.Ser349Cys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: SUFU NM_016169.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.15

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SUFU	NM_016169.4	c.1045A>T	p.Ser349Cys	missense_variant	Exon 9 of 12	ENST00000369902.8	NP_057253.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SUFU	ENST00000369902.8	c.1045A>T	p.Ser349Cys	missense_variant	Exon 9 of 12	1	NM_016169.4	ENSP00000358918.4
SUFU	ENST00000423559.2	c.1045A>T	p.Ser349Cys	missense_variant	Exon 9 of 10	1		ENSP00000411597.2
SUFU	ENST00000369899.6	c.1045A>T	p.Ser349Cys	missense_variant	Exon 9 of 11	1		ENSP00000358915.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Uncertain	0.034	T
BayesDel_noAF	Benign	-0.19
CADD	Uncertain	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.33	T;.;.
Eigen	Uncertain	0.62
Eigen_PC	Uncertain	0.63
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.97	D;D;D
M_CAP	Benign	0.034	D
MetaRNN	Uncertain	0.51	D;D;D
MetaSVM	Benign	-0.70	T
MutationAssessor	Benign	1.5	L;L;L
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-1.8	N;N;N
REVEL	Benign	0.20
Sift	Benign	0.059	T;T;D
Sift4G	Benign	0.071	T;T;D
Polyphen		1.0	D;D;D
Vest4		0.59
MutPred		0.40		Loss of phosphorylation at S349 (P = 0.0225);Loss of phosphorylation at S349 (P = 0.0225);Loss of phosphorylation at S349 (P = 0.0225);
MVP		0.31
MPC		1.6
ClinPred		0.89	D
GERP RS		5.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.18
gMVP		0.64

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: chr10-104375047;