rs1554742278

Variant names:

• chr9-98768171-G-T
• rs1554742278
• NM_173551.5:c.2052C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_173551.5(ANKS6):​c.2052C>A​(p.Ser684Arg) variant causes a missense 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. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ANKS6 NM_173551.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.49
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12723705).

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.2052C>A	p.Ser684Arg	missense	Exon 11 of 15	NP_775822.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKS6	ENST00000353234.5	TSL:1 MANE Select	c.2052C>A	p.Ser684Arg	missense	Exon 11 of 15	ENSP00000297837.6
	ANKS6	ENST00000375019.6	TSL:5	c.1149C>A	p.Ser383Arg	missense	Exon 10 of 15	ENSP00000364159.2
	ANKS6	ENST00000444472.5	TSL:2	c.456C>A	p.Ser152Arg	missense	Exon 4 of 9	ENSP00000398648.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Nephronophthisis 16 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.016	T
Eigen	Benign	-0.10
Eigen_PC	Benign	0.063
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.3	L
PhyloP100		1.5
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.060
Sift	Benign	0.39	T
Sift4G	Benign	0.11	T
Polyphen		0.0020	B
Vest4		0.25
MutPred		0.12		Loss of phosphorylation at S684 (P = 0.0118)
MVP		0.71
MPC		0.12
ClinPred		0.30	T
GERP RS		4.0
Varity_R		0.060
gMVP		0.29
Mutation Taster		=79/21	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: rs1554742278; hg19: chr9-101530453;