9-98796327-G-T

Variant names:

• chr9-98796327-G-T
• rs138948716
• NM_173551.5:c.165C>A

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_173551.5(ANKS6):​c.165C>A​(p.Ala55Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. A55A) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ANKS6 NM_173551.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.419
• Publications: 6 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BP7: Synonymous conserved (PhyloP=0.419 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANKS6	NM_173551.5	c.165C>A	p.Ala55Ala	synonymous_variant	Exon 1 of 15	ENST00000353234.5	NP_775822.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANKS6	ENST00000353234.5	c.165C>A	p.Ala55Ala	synonymous_variant	Exon 1 of 15	1	NM_173551.5	ENSP00000297837.6
ANKS6	ENST00000471846.1	n.213C>A		non_coding_transcript_exon_variant	Exon 1 of 2	2
ANKS6	ENST00000375019.6	c.-42+357C>A		intron_variant	Intron 1 of 14	5		ENSP00000364159.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1060206 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 502604

African (AFR) AF: 0.00 AC: 0 AN: 21702

American (AMR) AF: 0.00 AC: 0 AN: 7552

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12954

East Asian (EAS) AF: 0.00 AC: 0 AN: 24252

South Asian (SAS) AF: 0.00 AC: 0 AN: 20662

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 20696

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2762

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 907976

Other (OTH) AF: 0.00 AC: 0 AN: 41650

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	12
DANN	Benign	0.75
PhyloP100		0.42
PromoterAI		-0.031	Neutral
RBP_binding_hub_radar		1.1
RBP_regulation_power_radar		2.2

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: rs138948716; hg19: chr9-101558609;