rs1589969719

Variant names:

• chr10-102504157-C-A
• NM_016169.4:c.5C>A

Your query was ambiguous. Multiple possible variants found:

• chr10-102504157-C-A
• chr10-102504157-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_016169.4(SUFU):​c.5C>A​(p.Ala2Glu) 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. 12/21 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)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SUFU NM_016169.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.70

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19958335).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SUFU	NM_016169.4	c.5C>A	p.Ala2Glu	missense_variant	Exon 1 of 12	ENST00000369902.8	NP_057253.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SUFU	ENST00000369902.8	c.5C>A	p.Ala2Glu	missense_variant	Exon 1 of 12	1	NM_016169.4	ENSP00000358918.4
SUFU	ENST00000423559.2	c.5C>A	p.Ala2Glu	missense_variant	Exon 1 of 10	1		ENSP00000411597.2
SUFU	ENST00000369899.6	c.5C>A	p.Ala2Glu	missense_variant	Exon 1 of 11	1		ENSP00000358915.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1391248 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 686358

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.14	T;.;.
Eigen	Benign	-0.45
Eigen_PC	Benign	-0.16
FATHMM_MKL	Benign	0.48	N
LIST_S2	Benign	0.85	T;T;T
M_CAP	Pathogenic	0.48	D
MetaRNN	Benign	0.20	T;T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.0	N;N;N
PrimateAI	Pathogenic	0.89	D
PROVEAN	Benign	0.14	N;N;N
REVEL	Benign	0.085
Sift	Benign	0.22	T;T;T
Sift4G	Benign	1.0	T;T;T
Polyphen		0.0	B;B;B
Vest4		0.21
MutPred		0.19		Gain of solvent accessibility (P = 0.0145);Gain of solvent accessibility (P = 0.0145);Gain of solvent accessibility (P = 0.0145);
MVP		0.27
MPC		1.4
ClinPred		0.87	D
GERP RS		5.3
Varity_R		0.32
gMVP		0.31

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: chr10-104263914;