chr9-98796327-G-A

Variant names:

• chr9-98796327-G-A
• rs138948716
• NM_173551.5:c.165C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_173551.5(ANKS6):​c.165C>T​(p.Ala55Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.327 in 1,209,356 control chromosomes in the GnomAD database, including 66,736 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.28 (6599 hom., cov: 33)
  • Exomes 𝑓: 0.33 (60137 hom.)
• Consequence: ANKS6 NM_173551.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.419
• 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP6: Variant 9-98796327-G-A is Benign according to our data. Variant chr9-98796327-G-A is described in ClinVar as Benign. ClinVar VariationId is 262843.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.419 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.345 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKS6	NM_173551.5	MANE Select	c.165C>T	p.Ala55Ala	synonymous	Exon 1 of 15	NP_775822.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKS6	ENST00000353234.5	TSL:1 MANE Select	c.165C>T	p.Ala55Ala	synonymous	Exon 1 of 15	ENSP00000297837.6
	ANKS6	ENST00000471846.1	TSL:2	n.213C>T		non_coding_transcript_exon	Exon 1 of 2
	ANKS6	ENST00000375019.6	TSL:5	c.-42+357C>T		intron	N/A	ENSP00000364159.2

Frequencies

GnomAD3 genomes AF: 0.283 AC: 42190 AN: 149218 Hom.: 6594 Cov.: 33

Gnomad AFR AF: 0.137

Gnomad AMI AF: 0.344

Gnomad AMR AF: 0.288

Gnomad ASJ AF: 0.296

Gnomad EAS AF: 0.358

Gnomad SAS AF: 0.351

Gnomad FIN AF: 0.401

Gnomad MID AF: 0.312

Gnomad NFE AF: 0.341

Gnomad OTH AF: 0.287

GnomAD2 exomes AF: 0.438 AC: 402 AN: 918 AF XY: 0.438

Gnomad AFR exome AF: 0.375

Gnomad AMR exome AF: 0.471

Gnomad ASJ exome AF: 0.391

Gnomad EAS exome AF: 0.500

Gnomad FIN exome AF: 0.574

Gnomad NFE exome AF: 0.402

Gnomad OTH exome AF: 0.433

GnomAD4 exome AF: 0.333 AC: 353431 AN: 1060030 Hom.: 60137 Cov.: 32 AF XY: 0.335 AC XY: 168219 AN XY: 502518

African (AFR) AF: 0.125 AC: 2706 AN: 21696

American (AMR) AF: 0.316 AC: 2389 AN: 7550

Ashkenazi Jewish (ASJ) AF: 0.291 AC: 3774 AN: 12954

East Asian (EAS) AF: 0.436 AC: 10580 AN: 24242

South Asian (SAS) AF: 0.332 AC: 6861 AN: 20652

European-Finnish (FIN) AF: 0.399 AC: 8265 AN: 20690

Middle Eastern (MID) AF: 0.318 AC: 878 AN: 2762

European-Non Finnish (NFE) AF: 0.336 AC: 304918 AN: 907840

Other (OTH) AF: 0.314 AC: 13060 AN: 41644

GnomAD4 genome AF: 0.283 AC: 42202 AN: 149326 Hom.: 6599 Cov.: 33 AF XY: 0.286 AC XY: 20857 AN XY: 72826

African (AFR) AF: 0.137 AC: 5641 AN: 41190

American (AMR) AF: 0.289 AC: 4333 AN: 15010

Ashkenazi Jewish (ASJ) AF: 0.296 AC: 1015 AN: 3426

East Asian (EAS) AF: 0.359 AC: 1844 AN: 5142

South Asian (SAS) AF: 0.351 AC: 1695 AN: 4826

European-Finnish (FIN) AF: 0.401 AC: 3803 AN: 9480

Middle Eastern (MID) AF: 0.308 AC: 90 AN: 292

European-Non Finnish (NFE) AF: 0.341 AC: 22872 AN: 66982

Other (OTH) AF: 0.288 AC: 597 AN: 2070

Alfa AF: 0.203 Hom.: 505

Bravo AF: 0.270

Asia WGS AF: 0.369 AC: 1201 AN: 3264

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	ANKS6-related disorder (1)
-	-	1	Nephronophthisis 16 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	13
DANN	Benign	0.93
PhyloP100		0.42
PromoterAI		0.041	Neutral
RBP_binding_hub_radar		1.1
RBP_regulation_power_radar		2.2
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: rs138948716; hg19: chr9-101558609; COSMIC: COSV62050829; COSMIC: COSV62050829;