rs201821907

Variant names:

• chr9-98773967-C-A
• rs201821907
• NM_173551.5:c.1731G>T

Your query was ambiguous. Multiple possible variants found:

• chr9-98773967-C-A
• chr9-98773967-C-T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_173551.5(ANKS6):​c.1731G>T​(p.Thr577Thr) 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. T577T) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ANKS6 NM_173551.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.71
• 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: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (REVEL=0.023).
• BP7: Synonymous conserved (PhyloP=-3.71 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANKS6	NM_173551.5	c.1731G>T	p.Thr577Thr	synonymous_variant	Exon 9 of 15	ENST00000353234.5	NP_775822.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANKS6	ENST00000353234.5	c.1731G>T	p.Thr577Thr	synonymous_variant	Exon 9 of 15	1	NM_173551.5	ENSP00000297837.6
ANKS6	ENST00000375019.6	c.828G>T	p.Thr276Thr	synonymous_variant	Exon 8 of 15	5		ENSP00000364159.2
ANKS6	ENST00000444472.5	c.135G>T	p.Thr45Thr	synonymous_variant	Exon 2 of 9	2		ENSP00000398648.1
ANKS6	ENST00000634393.1	n.831G>T		non_coding_transcript_exon_variant	Exon 7 of 15	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00 AC: 0 AN: 235564 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	0.020
DANN	Benign	0.58
PhyloP100		-3.7
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

Other links and lift over

dbSNP: rs201821907; hg19: chr9-101536249;