rs115965425

Variant names:

• chr9-98790084-C-T
• rs115965425
• NM_173551.5:c.862+20G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_173551.5(ANKS6):​c.862+20G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00117 in 1,537,674 control chromosomes in the GnomAD database, including 15 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0064 (9 hom., cov: 32)
  • Exomes 𝑓: 0.00059 (6 hom.)
• Consequence: ANKS6 NM_173551.5 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.274
• Publications: 1 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: Labcorp Genetics (formerly Invitae), ClinGen
• 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=-0.94).
• BP6: Variant 9-98790084-C-T is Benign according to our data. Variant chr9-98790084-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 262857.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00643 (979/152308) while in subpopulation AFR AF = 0.0221 (918/41552). AF 95% confidence interval is 0.0209. There are 9 homozygotes in GnomAd4. There are 490 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 9 AR gene

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.862+20G>A		intron	N/A	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.862+20G>A		intron	N/A	ENSP00000297837.6	Q68DC2-1
	ANKS6	ENST00000941017.1		c.862+20G>A		intron	N/A	ENSP00000611076.1
	ANKS6	ENST00000927508.1		c.862+20G>A		intron	N/A	ENSP00000597567.1

Frequencies

GnomAD3 genomes AF: 0.00642 AC: 977 AN: 152190 Hom.: 9 Cov.: 32

Gnomad AFR AF: 0.0221

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00262

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00718

GnomAD2 exomes AF: 0.00196 AC: 391 AN: 199334 AF XY: 0.00159

Gnomad AFR exome AF: 0.0229

Gnomad AMR exome AF: 0.00136

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000118

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000326

Gnomad OTH exome AF: 0.00107

GnomAD4 exome AF: 0.000590 AC: 817 AN: 1385366 Hom.: 6 Cov.: 31 AF XY: 0.000554 AC XY: 376 AN XY: 678196

African (AFR) AF: 0.0201 AC: 635 AN: 31666

American (AMR) AF: 0.00175 AC: 64 AN: 36602

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21406

East Asian (EAS) AF: 0.0000517 AC: 2 AN: 38654

South Asian (SAS) AF: 0.000106 AC: 8 AN: 75776

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5284

European-Non Finnish (NFE) AF: 0.0000206 AC: 22 AN: 1068328

Other (OTH) AF: 0.00151 AC: 86 AN: 57042

GnomAD4 genome AF: 0.00643 AC: 979 AN: 152308 Hom.: 9 Cov.: 32 AF XY: 0.00658 AC XY: 490 AN XY: 74472

African (AFR) AF: 0.0221 AC: 918 AN: 41552

American (AMR) AF: 0.00261 AC: 40 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68028

Other (OTH) AF: 0.00711 AC: 15 AN: 2110

Alfa AF: 0.00249 Hom.: 0

Bravo AF: 0.00720

Asia WGS AF: 0.00173 AC: 6 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	Nephronophthisis 16 (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.0010
DANN	Benign	0.67
PhyloP100		-0.27
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism

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: rs115965425; hg19: chr9-101552366; COSMIC: COSV100782255;