chr9-98736257-T-A

Position:

• chr9-98736257-T-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_173551.5(ANKS6):​c.*262A>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 0.0344 in 1,296,300 control chromosomes in the GnomAD database, including 2,000 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.040 (368 hom., cov: 32)
  • Exomes 𝑓: 0.034 (1632 hom.)
• Consequence: ANKS6 NM_173551.5 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.165

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 9-98736257-T-A is Benign according to our data. Variant chr9-98736257-T-A is described in ClinVar as [Likely_benign]. Clinvar id is 1190217.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.251 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANKS6	NM_173551.5	c.*262A>T		3_prime_UTR_variant	15/15	ENST00000353234.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANKS6	ENST00000353234.5	c.*262A>T		3_prime_UTR_variant	15/15	1	NM_173551.5	P1
ANKS6	ENST00000375019.6	c.1705+270A>T		intron_variant		5
ANKS6	ENST00000444472.5	c.*23+239A>T		intron_variant		2
ANKS6	ENST00000634393.1	n.1743+270A>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0395 AC: 5991 AN: 151764 Hom.: 363 Cov.: 32

Gnomad AFR AF: 0.00670

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.108

Gnomad ASJ AF: 0.0392

Gnomad EAS AF: 0.262

Gnomad SAS AF: 0.106

Gnomad FIN AF: 0.00966

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0279

Gnomad OTH AF: 0.0383

GnomAD4 exome AF: 0.0337 AC: 38602 AN: 1144418 Hom.: 1632 Cov.: 29 AF XY: 0.0346 AC XY: 18880 AN XY: 545472

Gnomad4 AFR exome AF: 0.00498

Gnomad4 AMR exome AF: 0.141

Gnomad4 ASJ exome AF: 0.0379

Gnomad4 EAS exome AF: 0.255

Gnomad4 SAS exome AF: 0.0981

Gnomad4 FIN exome AF: 0.00795

Gnomad4 NFE exome AF: 0.0245

Gnomad4 OTH exome AF: 0.0423

GnomAD4 genome AF: 0.0395 AC: 6001 AN: 151882 Hom.: 368 Cov.: 32 AF XY: 0.0423 AC XY: 3138 AN XY: 74204

Gnomad4 AFR AF: 0.00668

Gnomad4 AMR AF: 0.108

Gnomad4 ASJ AF: 0.0392

Gnomad4 EAS AF: 0.262

Gnomad4 SAS AF: 0.105

Gnomad4 FIN AF: 0.00966

Gnomad4 NFE AF: 0.0278

Gnomad4 OTH AF: 0.0398

Alfa AF: 0.0275 Hom.: 20

Bravo AF: 0.0478

Asia WGS AF: 0.145 AC: 507 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 25, 2019	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.6
DANN	Benign	0.62

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

Publications

LitVar

Other links and lift over

dbSNP: rs337585; hg19: chr9-101498539; COSMIC: COSV62048741;