10-102604895-G-A

Variant names:

• chr10-102604895-G-A
• rs10786691
• NM_016169.4:c.1022+5351G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016169.4(SUFU):​c.1022+5351G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.456 in 145,972 control chromosomes in the GnomAD database, including 15,434 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.46 (15434 hom., cov: 26)
• Consequence: SUFU NM_016169.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.82
• Publications: 14 publications found

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]

SUFU Gene-Disease associations (from GenCC):

• medulloblastoma

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), ClinGen
• nevoid basal cell carcinoma syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Illumina, Genomics England PanelApp
• basal cell nevus syndrome 2

  Inheritance: AD Classification: STRONG Submitted by: G2P
• ocular motor apraxia, Cogan type

  Inheritance: AD Classification: STRONG Submitted by: Franklin by Genoox
• Joubert syndrome 32

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
• Joubert syndrome

  Inheritance: AR, AD Classification: MODERATE, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics
• apraxia

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
• ciliopathy

  Inheritance: AR Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.657 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SUFU	NM_016169.4	c.1022+5351G>A		intron_variant	Intron 8 of 11	ENST00000369902.8	NP_057253.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SUFU	ENST00000369902.8	c.1022+5351G>A		intron_variant	Intron 8 of 11	1	NM_016169.4	ENSP00000358918.4
SUFU	ENST00000423559.2	c.1022+5351G>A		intron_variant	Intron 8 of 9	1		ENSP00000411597.2
SUFU	ENST00000369899.6	c.1022+5351G>A		intron_variant	Intron 8 of 10	1		ENSP00000358915.2

Frequencies

GnomAD3 genomes AF: 0.456 AC: 66575 AN: 145894 Hom.: 15408 Cov.: 26

Gnomad AFR AF: 0.452

Gnomad AMI AF: 0.532

Gnomad AMR AF: 0.550

Gnomad ASJ AF: 0.319

Gnomad EAS AF: 0.677

Gnomad SAS AF: 0.518

Gnomad FIN AF: 0.450

Gnomad MID AF: 0.375

Gnomad NFE AF: 0.425

Gnomad OTH AF: 0.446

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.456 AC: 66628 AN: 145972 Hom.: 15434 Cov.: 26 AF XY: 0.462 AC XY: 32583 AN XY: 70476

African (AFR) AF: 0.452 AC: 17732 AN: 39198

American (AMR) AF: 0.551 AC: 8038 AN: 14580

Ashkenazi Jewish (ASJ) AF: 0.319 AC: 1091 AN: 3424

East Asian (EAS) AF: 0.677 AC: 3361 AN: 4968

South Asian (SAS) AF: 0.519 AC: 2401 AN: 4630

European-Finnish (FIN) AF: 0.450 AC: 3983 AN: 8850

Middle Eastern (MID) AF: 0.376 AC: 103 AN: 274

European-Non Finnish (NFE) AF: 0.425 AC: 28538 AN: 67126

Other (OTH) AF: 0.446 AC: 905 AN: 2028

Alfa AF: 0.427 Hom.: 1801

Bravo AF: 0.465

Asia WGS AF: 0.598 AC: 2077 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	5.0
DANN	Benign	0.34
PhyloP100		1.8
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10786691; hg19: chr10-104364652;