NM_016169.4:c.318-6794G>A

Variant names:

• chr10-102543176-G-A
• rs11191325
• NM_016169.4:c.318-6794G>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.318-6794G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.305 in 151,900 control chromosomes in the GnomAD database, including 7,330 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 0.30 (7330 hom., cov: 32)
• Consequence: SUFU NM_016169.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.209
• Publications: 12 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.349 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016169.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SUFU	NM_016169.4	MANE Select	c.318-6794G>A		intron	N/A	NP_057253.2
	SUFU	NM_001178133.2		c.318-6794G>A		intron	N/A	NP_001171604.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SUFU	ENST00000369902.8	TSL:1 MANE Select	c.318-6794G>A		intron	N/A	ENSP00000358918.4
	SUFU	ENST00000423559.2	TSL:1	c.318-6794G>A		intron	N/A	ENSP00000411597.2
	SUFU	ENST00000369899.6	TSL:1	c.318-6794G>A		intron	N/A	ENSP00000358915.2

Frequencies

GnomAD3 genomes AF: 0.305 AC: 46242 AN: 151784 Hom.: 7329 Cov.: 32

Gnomad AFR AF: 0.235

Gnomad AMI AF: 0.402

Gnomad AMR AF: 0.356

Gnomad ASJ AF: 0.253

Gnomad EAS AF: 0.260

Gnomad SAS AF: 0.287

Gnomad FIN AF: 0.378

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.331

Gnomad OTH AF: 0.285

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

GnomAD4 genome AF: 0.305 AC: 46256 AN: 151900 Hom.: 7330 Cov.: 32 AF XY: 0.308 AC XY: 22835 AN XY: 74222

African (AFR) AF: 0.235 AC: 9717 AN: 41428

American (AMR) AF: 0.356 AC: 5439 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.253 AC: 877 AN: 3464

East Asian (EAS) AF: 0.260 AC: 1342 AN: 5162

South Asian (SAS) AF: 0.287 AC: 1381 AN: 4818

European-Finnish (FIN) AF: 0.378 AC: 3975 AN: 10502

Middle Eastern (MID) AF: 0.262 AC: 77 AN: 294

European-Non Finnish (NFE) AF: 0.331 AC: 22489 AN: 67958

Other (OTH) AF: 0.282 AC: 594 AN: 2106

Alfa AF: 0.321 Hom.: 3942

Bravo AF: 0.301

Asia WGS AF: 0.285 AC: 994 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.2
DANN	Benign	0.82
PhyloP100		-0.21
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: rs11191325; hg19: chr10-104302933;