9-98736327-T-C

Position:

• chr9-98736327-T-C

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.*192A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00955 in 1,418,540 control chromosomes in the GnomAD database, including 1,049 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.049 (577 hom., cov: 32)
  • Exomes 𝑓: 0.0048 (472 hom.)
• Consequence: ANKS6 NM_173551.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.49

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=-0.89).
• BP6: Variant 9-98736327-T-C is Benign according to our data. Variant chr9-98736327-T-C is described in ClinVar as [Benign]. Clinvar id is 1250349.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.168 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANKS6	NM_173551.5	c.*192A>G		3_prime_UTR_variant	15/15	ENST00000353234.5	NP_775822.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANKS6	ENST00000353234.5	c.*192A>G		3_prime_UTR_variant	15/15	1	NM_173551.5	ENSP00000297837	P1
ANKS6	ENST00000375019.6	c.1705+200A>G		intron_variant		5		ENSP00000364159
ANKS6	ENST00000444472.5	c.*23+169A>G		intron_variant		2		ENSP00000398648
ANKS6	ENST00000634393.1	n.1743+200A>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0489 AC: 7436 AN: 151944 Hom.: 569 Cov.: 32

Gnomad AFR AF: 0.171

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0172

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000529

Gnomad OTH AF: 0.0306

GnomAD4 exome AF: 0.00479 AC: 6071 AN: 1266478 Hom.: 472 Cov.: 32 AF XY: 0.00427 AC XY: 2610 AN XY: 611926

Gnomad4 AFR exome AF: 0.180

Gnomad4 AMR exome AF: 0.0112

Gnomad4 ASJ exome AF: 0.0000540

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000423

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000274

Gnomad4 OTH exome AF: 0.0102

GnomAD4 genome AF: 0.0491 AC: 7471 AN: 152062 Hom.: 577 Cov.: 32 AF XY: 0.0470 AC XY: 3497 AN XY: 74346

Gnomad4 AFR AF: 0.172

Gnomad4 AMR AF: 0.0172

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000415

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000529

Gnomad4 OTH AF: 0.0303

Alfa AF: 0.0241 Hom.: 57

Bravo AF: 0.0572

Asia WGS AF: 0.0100 AC: 36 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 10, 2020	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.41
DANN	Benign	0.37

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: rs61383603; hg19: chr9-101498609;