rs375604399

Variant names:

• chr9-98784173-G-A
• rs375604399
• NM_173551.5:c.908-16C>T

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_173551.5(ANKS6):​c.908-16C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000268 in 1,512,354 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00026 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00027 (3 hom.)
• Consequence: ANKS6 NM_173551.5 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.630
• Publications: 0 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 -16 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 9-98784173-G-A is Benign according to our data. Variant chr9-98784173-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 262858.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAdExome4 at 3 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKS6	NM_173551.5	MANE Select	c.908-16C>T		intron	N/A	NP_775822.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKS6	ENST00000353234.5	TSL:1 MANE Select	c.908-16C>T		intron	N/A	ENSP00000297837.6
	ANKS6	ENST00000375019.6	TSL:5	c.5-16C>T		intron	N/A	ENSP00000364159.2
	ANKS6	ENST00000466120.1	TSL:2	n.439-16C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.000250 AC: 38 AN: 152142 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000456

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000379 AC: 68 AN: 179488 AF XY: 0.000450

Gnomad AFR exome AF: 0.0000771

Gnomad AMR exome AF: 0.000126

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000494

Gnomad OTH exome AF: 0.000772

GnomAD4 exome AF: 0.000269 AC: 366 AN: 1360094 Hom.: 3 Cov.: 30 AF XY: 0.000311 AC XY: 207 AN XY: 665402

African (AFR) AF: 0.000133 AC: 4 AN: 30136

American (AMR) AF: 0.0000879 AC: 3 AN: 34128

Ashkenazi Jewish (ASJ) AF: 0.0000470 AC: 1 AN: 21298

East Asian (EAS) AF: 0.00 AC: 0 AN: 35930

South Asian (SAS) AF: 0.00138 AC: 99 AN: 71536

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50744

Middle Eastern (MID) AF: 0.00131 AC: 7 AN: 5348

European-Non Finnish (NFE) AF: 0.000226 AC: 238 AN: 1054978

Other (OTH) AF: 0.000250 AC: 14 AN: 55996

GnomAD4 genome AF: 0.000256 AC: 39 AN: 152260 Hom.: 0 Cov.: 31 AF XY: 0.000242 AC XY: 18 AN XY: 74452

African (AFR) AF: 0.00 AC: 0 AN: 41558

American (AMR) AF: 0.0000654 AC: 1 AN: 15292

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5160

South Asian (SAS) AF: 0.00124 AC: 6 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

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

European-Non Finnish (NFE) AF: 0.000456 AC: 31 AN: 68026

Other (OTH) AF: 0.000473 AC: 1 AN: 2114

Alfa AF: 0.000431 Hom.: 0

Bravo AF: 0.000204

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	Nephronophthisis 16 (2)
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.2
DANN	Benign	0.66
PhyloP100		0.63
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs375604399; hg19: chr9-101546455;