NM_016169.4:c.318-16118A>G

Variant names:

• chr10-102533852-A-G
• rs10748825
• NM_016169.4:c.318-16118A>G

Variant summary

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

The NM_016169.4(SUFU):​c.318-16118A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.348 in 152,088 control chromosomes in the GnomAD database, including 9,401 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 0.35 (9401 hom., cov: 32)
• Consequence: SUFU NM_016169.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.269
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.384 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SUFU	NM_016169.4	c.318-16118A>G		intron_variant	Intron 2 of 11	ENST00000369902.8	NP_057253.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SUFU	ENST00000369902.8	c.318-16118A>G		intron_variant	Intron 2 of 11	1	NM_016169.4	ENSP00000358918.4
SUFU	ENST00000423559.2	c.318-16118A>G		intron_variant	Intron 2 of 9	1		ENSP00000411597.2
SUFU	ENST00000369899.6	c.318-16118A>G		intron_variant	Intron 2 of 10	1		ENSP00000358915.2

Frequencies

GnomAD3 genomes AF: 0.348 AC: 52959 AN: 151968 Hom.: 9390 Cov.: 32

Gnomad AFR AF: 0.389

Gnomad AMI AF: 0.405

Gnomad AMR AF: 0.370

Gnomad ASJ AF: 0.255

Gnomad EAS AF: 0.260

Gnomad SAS AF: 0.287

Gnomad FIN AF: 0.377

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.331

Gnomad OTH AF: 0.313

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

GnomAD4 genome AF: 0.348 AC: 52991 AN: 152088 Hom.: 9401 Cov.: 32 AF XY: 0.350 AC XY: 26003 AN XY: 74352

African (AFR) AF: 0.389 AC: 16111 AN: 41466

American (AMR) AF: 0.371 AC: 5662 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.255 AC: 883 AN: 3468

East Asian (EAS) AF: 0.260 AC: 1343 AN: 5172

South Asian (SAS) AF: 0.287 AC: 1381 AN: 4816

European-Finnish (FIN) AF: 0.377 AC: 3981 AN: 10568

Middle Eastern (MID) AF: 0.289 AC: 85 AN: 294

European-Non Finnish (NFE) AF: 0.331 AC: 22526 AN: 68010

Other (OTH) AF: 0.310 AC: 654 AN: 2110

Alfa AF: 0.343 Hom.: 1493

Bravo AF: 0.352

Asia WGS AF: 0.294 AC: 1027 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.6
DANN	Benign	0.67
PhyloP100		0.27
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: rs10748825; hg19: chr10-104293609;