NM_173551.5:c.*199C>G

Variant names:

• chr9-98736320-G-C
• rs75690065
• NM_173551.5:c.*199C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_173551.5(ANKS6):​c.*199C>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 0.00000318 in 1,259,110 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000032 (0 hom.)
• Consequence: ANKS6 NM_173551.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.82
• Publications: 1 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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKS6	NM_173551.5	MANE Select	c.*199C>G		3_prime_UTR	Exon 15 of 15	NP_775822.3	Q68DC2-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKS6	ENST00000353234.5	TSL:1 MANE Select	c.*199C>G		3_prime_UTR	Exon 15 of 15	ENSP00000297837.6	Q68DC2-1
	ANKS6	ENST00000941017.1		c.*199C>G		3_prime_UTR	Exon 13 of 13	ENSP00000611076.1
	ANKS6	ENST00000927508.1		c.*199C>G		3_prime_UTR	Exon 13 of 13	ENSP00000597567.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000318 AC: 4 AN: 1259110 Hom.: 0 Cov.: 32 AF XY: 0.00000658 AC XY: 4 AN XY: 607760

African (AFR) AF: 0.00 AC: 0 AN: 27722

American (AMR) AF: 0.0000567 AC: 1 AN: 17648

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18342

East Asian (EAS) AF: 0.00 AC: 0 AN: 33580

South Asian (SAS) AF: 0.00 AC: 0 AN: 57532

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 29270

Middle Eastern (MID) AF: 0.000283 AC: 1 AN: 3538

European-Non Finnish (NFE) AF: 9.81e-7 AC: 1 AN: 1019238

Other (OTH) AF: 0.0000191 AC: 1 AN: 52240

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.9
DANN	Benign	0.39
PhyloP100		1.8

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs75690065; hg19: chr9-101498602;