9-98773967-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 2P and 13B. PM2 BP4_Strong BP6_Very_Strong BP7

The NM_173551.5(ANKS6):c.1731G>A(p.Thr577=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000404 in 1,599,386 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00021 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00042 (1 hom.)
• Consequence: ANKS6 NM_173551.5 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -3.71

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 -11 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant 9-98773967-C-T is Benign according to our data. Variant chr9-98773967-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 474443.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-3.71 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANKS6	NM_173551.5	c.1731G>A	p.Thr577=	synonymous_variant	9/15	ENST00000353234.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANKS6	ENST00000353234.5	c.1731G>A	p.Thr577=	synonymous_variant	9/15	1	NM_173551.5	P1
ANKS6	ENST00000375019.6	c.828G>A	p.Thr276=	synonymous_variant	8/15	5
ANKS6	ENST00000444472.5	c.138G>A	p.Thr46=	synonymous_variant	2/9	2
ANKS6	ENST00000634393.1	n.831G>A		non_coding_transcript_exon_variant	7/15	5

Frequencies

GnomAD3 genomes AF: 0.000211 AC: 32 AN: 151550 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.000398

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000166 AC: 39 AN: 235564 Hom.: 0 AF XY: 0.000195 AC XY: 25 AN XY: 128338

Gnomad AFR exome AF: 0.000137

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000173

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000293

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000424 AC: 614 AN: 1447836 Hom.: 1 Cov.: 32 AF XY: 0.000387 AC XY: 279 AN XY: 720228

Gnomad4 AFR exome AF: 0.000152

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000201

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000517

Gnomad4 OTH exome AF: 0.000334

GnomAD4 genome AF: 0.000211 AC: 32 AN: 151550 Hom.: 0 Cov.: 32 AF XY: 0.000189 AC XY: 14 AN XY: 73984

Gnomad4 AFR AF: 0.000121

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000398

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000171 Hom.: 0

Bravo AF: 0.000174

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Nephronophthisis 16 Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Fulgent Genetics, Fulgent Genetics	Oct 27, 2021	- -
Likely benign, criteria provided, single submitter	clinical testing	Invitae	Dec 15, 2022	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
Cadd	Benign	0.12
Dann	Benign	0.61
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8

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: rs201821907; hg19: chr9-101536249; COSMIC: COSV62049730;