chr9-98796162-G-A

Variant names:

• chr9-98796162-G-A
• rs76903503
• NM_173551.5:c.330C>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.330C>T​(p.Tyr110Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.117 in 1,412,228 control chromosomes in the GnomAD database, including 10,695 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.11 (1097 hom., cov: 33)
  • Exomes 𝑓: 0.12 (9598 hom.)
• Consequence: ANKS6 NM_173551.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 1.94
• Publications: 12 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=-0.53).
• BP6: Variant 9-98796162-G-A is Benign according to our data. Variant chr9-98796162-G-A is described in ClinVar as Benign. ClinVar VariationId is 262851.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.94 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.205 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.330C>T	p.Tyr110Tyr	synonymous	Exon 1 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.330C>T	p.Tyr110Tyr	synonymous	Exon 1 of 15	ENSP00000297837.6	Q68DC2-1
	ANKS6	ENST00000941017.1		c.330C>T	p.Tyr110Tyr	synonymous	Exon 1 of 13	ENSP00000611076.1
	ANKS6	ENST00000927508.1		c.330C>T	p.Tyr110Tyr	synonymous	Exon 1 of 13	ENSP00000597567.1

Frequencies

GnomAD3 genomes AF: 0.106 AC: 16112 AN: 151990 Hom.: 1095 Cov.: 33

Gnomad AFR AF: 0.0374

Gnomad AMI AF: 0.126

Gnomad AMR AF: 0.155

Gnomad ASJ AF: 0.0905

Gnomad EAS AF: 0.216

Gnomad SAS AF: 0.147

Gnomad FIN AF: 0.190

Gnomad MID AF: 0.105

Gnomad NFE AF: 0.113

Gnomad OTH AF: 0.114

GnomAD2 exomes AF: 0.141 AC: 7877 AN: 55872 AF XY: 0.137

Gnomad AFR exome AF: 0.0478

Gnomad AMR exome AF: 0.205

Gnomad ASJ exome AF: 0.0848

Gnomad EAS exome AF: 0.208

Gnomad FIN exome AF: 0.190

Gnomad NFE exome AF: 0.112

Gnomad OTH exome AF: 0.123

GnomAD4 exome AF: 0.119 AC: 149385 AN: 1260130 Hom.: 9598 Cov.: 30 AF XY: 0.119 AC XY: 73681 AN XY: 618334

African (AFR) AF: 0.0313 AC: 804 AN: 25704

American (AMR) AF: 0.191 AC: 3923 AN: 20556

Ashkenazi Jewish (ASJ) AF: 0.0817 AC: 1738 AN: 21264

East Asian (EAS) AF: 0.226 AC: 6206 AN: 27502

South Asian (SAS) AF: 0.144 AC: 9014 AN: 62802

European-Finnish (FIN) AF: 0.185 AC: 5760 AN: 31102

Middle Eastern (MID) AF: 0.119 AC: 453 AN: 3814

European-Non Finnish (NFE) AF: 0.113 AC: 115169 AN: 1015872

Other (OTH) AF: 0.123 AC: 6318 AN: 51514

GnomAD4 genome AF: 0.106 AC: 16118 AN: 152098 Hom.: 1097 Cov.: 33 AF XY: 0.111 AC XY: 8259 AN XY: 74354

African (AFR) AF: 0.0374 AC: 1552 AN: 41544

American (AMR) AF: 0.155 AC: 2374 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0905 AC: 314 AN: 3468

East Asian (EAS) AF: 0.216 AC: 1107 AN: 5128

South Asian (SAS) AF: 0.147 AC: 708 AN: 4830

European-Finnish (FIN) AF: 0.190 AC: 2011 AN: 10560

Middle Eastern (MID) AF: 0.110 AC: 32 AN: 292

European-Non Finnish (NFE) AF: 0.113 AC: 7668 AN: 67970

Other (OTH) AF: 0.112 AC: 237 AN: 2112

Alfa AF: 0.107 Hom.: 147

Bravo AF: 0.104

Asia WGS AF: 0.194 AC: 670 AN: 3464

ClinVar

ClinVar submissions

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	-0.53
CADD	Benign	11
DANN	Uncertain	0.97
PhyloP100		1.9
PromoterAI		0.15	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
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: rs76903503; hg19: chr9-101558444; COSMIC: COSV62050373; COSMIC: COSV62050373;