9-98736282-C-G

Variant names:

• chr9-98736282-C-G
• rs10760479
• NM_173551.5:c.*237G>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_173551.5(ANKS6):​c.*237G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.699 in 1,347,724 control chromosomes in the GnomAD database, including 335,108 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.64 (31622 hom., cov: 29)
  • Exomes 𝑓: 0.71 (303486 hom.)
• Consequence: ANKS6 NM_173551.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.214
• Publications: 6 publications found

Genes affected

ANKS6 (HGNC:26724): (ankyrin repeat and sterile alpha motif domain containing 6) This gene encodes a protein containing multiple ankyrin repeats and a SAM domain. It is thought that this protein may localize to the proximal region of the primary cilium, and may play a role in renal and cardiovascular development. Mutations in this gene have been shown to cause a form of nephronophthisis (NPHP16), a chronic tubulo-interstitial nephritis. [provided by RefSeq, Jul 2015]

ANKS6 Gene-Disease associations (from GenCC):

• nephronophthisis 16

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: ClinGen, Labcorp Genetics (formerly Invitae)
• nephronophthisis 1

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• nephronophthisis 2

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 9-98736282-C-G is Benign according to our data. Variant chr9-98736282-C-G is described in ClinVar as Benign. ClinVar VariationId is 1279257.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.722 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173551.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKS6	NM_173551.5	MANE Select	c.*237G>C		3_prime_UTR	Exon 15 of 15	NP_775822.3	Q68DC2-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKS6	ENST00000353234.5	TSL:1 MANE Select	c.*237G>C		3_prime_UTR	Exon 15 of 15	ENSP00000297837.6	Q68DC2-1
	ANKS6	ENST00000941017.1		c.*237G>C		3_prime_UTR	Exon 13 of 13	ENSP00000611076.1
	ANKS6	ENST00000927508.1		c.*237G>C		3_prime_UTR	Exon 13 of 13	ENSP00000597567.1

Frequencies

GnomAD3 genomes AF: 0.637 AC: 96472 AN: 151518 Hom.: 31622 Cov.: 29

Gnomad AFR AF: 0.514

Gnomad AMI AF: 0.771

Gnomad AMR AF: 0.629

Gnomad ASJ AF: 0.750

Gnomad EAS AF: 0.354

Gnomad SAS AF: 0.584

Gnomad FIN AF: 0.647

Gnomad MID AF: 0.718

Gnomad NFE AF: 0.727

Gnomad OTH AF: 0.679

GnomAD4 exome AF: 0.707 AC: 846178 AN: 1196088 Hom.: 303486 Cov.: 43 AF XY: 0.706 AC XY: 404954 AN XY: 573616

African (AFR) AF: 0.504 AC: 13200 AN: 26176

American (AMR) AF: 0.592 AC: 8339 AN: 14094

Ashkenazi Jewish (ASJ) AF: 0.757 AC: 12724 AN: 16818

East Asian (EAS) AF: 0.313 AC: 9423 AN: 30096

South Asian (SAS) AF: 0.609 AC: 27673 AN: 45436

European-Finnish (FIN) AF: 0.659 AC: 16636 AN: 25262

Middle Eastern (MID) AF: 0.724 AC: 2405 AN: 3320

European-Non Finnish (NFE) AF: 0.732 AC: 721571 AN: 985578

Other (OTH) AF: 0.694 AC: 34207 AN: 49308

GnomAD4 genome AF: 0.636 AC: 96494 AN: 151636 Hom.: 31622 Cov.: 29 AF XY: 0.631 AC XY: 46740 AN XY: 74052

African (AFR) AF: 0.514 AC: 21200 AN: 41282

American (AMR) AF: 0.627 AC: 9554 AN: 15226

Ashkenazi Jewish (ASJ) AF: 0.750 AC: 2604 AN: 3470

East Asian (EAS) AF: 0.354 AC: 1816 AN: 5134

South Asian (SAS) AF: 0.585 AC: 2801 AN: 4788

European-Finnish (FIN) AF: 0.647 AC: 6762 AN: 10454

Middle Eastern (MID) AF: 0.718 AC: 211 AN: 294

European-Non Finnish (NFE) AF: 0.727 AC: 49424 AN: 67976

Other (OTH) AF: 0.676 AC: 1419 AN: 2100

Alfa AF: 0.594 Hom.: 1978

Bravo AF: 0.625

Asia WGS AF: 0.472 AC: 1642 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.9
DANN	Benign	0.79
PhyloP100		0.21
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.1
Mutation Taster		=99/1	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: rs10760479; hg19: chr9-101498564;