rs75690065

Variant names:

• chr9-98736320-G-A
• rs75690065
• NM_173551.5:c.*199C>T

Your query was ambiguous. Multiple possible variants found:

• chr9-98736320-G-A
• chr9-98736320-G-C

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.*199C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00227 in 1,411,292 control chromosomes in the GnomAD database, including 56 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.012 (35 hom., cov: 32)
  • Exomes 𝑓: 0.0011 (21 hom.)
• Consequence: ANKS6 NM_173551.5 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.82
• 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: 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=-0.82).
• BP6: Variant 9-98736320-G-A is Benign according to our data. Variant chr9-98736320-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 1328662.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 = 0.0117 (1778/152186) while in subpopulation AFR AF = 0.0412 (1710/41522). AF 95% confidence interval is 0.0396. There are 35 homozygotes in GnomAd4. There are 817 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 35 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.*199C>T		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.*199C>T		3_prime_UTR	Exon 15 of 15	ENSP00000297837.6	Q68DC2-1
	ANKS6	ENST00000941017.1		c.*199C>T		3_prime_UTR	Exon 13 of 13	ENSP00000611076.1
	ANKS6	ENST00000927508.1		c.*199C>T		3_prime_UTR	Exon 13 of 13	ENSP00000597567.1

Frequencies

GnomAD3 genomes AF: 0.0117 AC: 1779 AN: 152068 Hom.: 35 Cov.: 32

Gnomad AFR AF: 0.0413

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00314

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00766

GnomAD4 exome AF: 0.00113 AC: 1425 AN: 1259106 Hom.: 21 Cov.: 32 AF XY: 0.000995 AC XY: 605 AN XY: 607760

African (AFR) AF: 0.0436 AC: 1208 AN: 27718

American (AMR) AF: 0.00227 AC: 40 AN: 17648

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18342

East Asian (EAS) AF: 0.00 AC: 0 AN: 33580

South Asian (SAS) AF: 0.0000348 AC: 2 AN: 57532

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 29270

Middle Eastern (MID) AF: 0.000283 AC: 1 AN: 3538

European-Non Finnish (NFE) AF: 0.0000157 AC: 16 AN: 1019238

Other (OTH) AF: 0.00302 AC: 158 AN: 52240

GnomAD4 genome AF: 0.0117 AC: 1778 AN: 152186 Hom.: 35 Cov.: 32 AF XY: 0.0110 AC XY: 817 AN XY: 74390

African (AFR) AF: 0.0412 AC: 1710 AN: 41522

American (AMR) AF: 0.00314 AC: 48 AN: 15288

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5156

South Asian (SAS) AF: 0.00 AC: 0 AN: 4812

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10590

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

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

Other (OTH) AF: 0.00758 AC: 16 AN: 2112

Alfa AF: 0.00312 Hom.: 2

Bravo AF: 0.0131

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely 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	-0.82
CADD	Benign	4.9
DANN	Benign	0.48
PhyloP100		1.8
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: rs75690065; hg19: chr9-101498602;