9-98736519-T-TCACG

Variant names:

• chr9-98736519-T-TCACG
• NM_173551.5:c.2612_2615dupCGTG

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PM4

The NM_173551.5(ANKS6):​c.2612_2615dupCGTG​(p.Ter872CysfsTer87) variant causes a frameshift, stop lost change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ANKS6 NM_173551.5 frameshift, stop_lost
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.06

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 Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Stoplost variant in NM_173551.5 Downstream stopcodon found after 892 codons.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANKS6	NM_173551.5	c.2612_2615dupCGTG	p.Ter872CysfsTer87	frameshift_variant, stop_lost	Exon 15 of 15	ENST00000353234.5	NP_775822.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANKS6	ENST00000353234.5	c.2612_2615dupCGTG	p.Ter872CysfsTer87	frameshift_variant, stop_lost	Exon 15 of 15	1	NM_173551.5	ENSP00000297837.6
ANKS6	ENST00000444472.5	c.1019_1022dupCGTG	p.Ter341fs	frameshift_variant, stop_lost	Exon 8 of 9	2		ENSP00000398648.1
ANKS6	ENST00000375019.6	c.1705+4_1705+7dupCGTG		splice_region_variant, intron_variant	Intron 14 of 14	5		ENSP00000364159.2
ANKS6	ENST00000634393.1	n.1743+4_1743+7dupCGTG		splice_region_variant, intron_variant	Intron 14 of 14	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Nephronophthisis 16 Uncertain:1

Mar 01, 2024

Fulgent Genetics, Fulgent Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-101498801;