9-98770938-C-G

Position:

• chr9-98770938-C-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_173551.5(ANKS6):​c.1930G>C​(p.Val644Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000209 in 1,434,246 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict 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: 34)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: ANKS6 NM_173551.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.31

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.053862035).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANKS6	NM_173551.5	c.1930G>C	p.Val644Leu	missense_variant	10/15	ENST00000353234.5	NP_775822.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANKS6	ENST00000353234.5	c.1930G>C	p.Val644Leu	missense_variant	10/15	1	NM_173551.5	ENSP00000297837	P1
ANKS6	ENST00000375019.6	c.1027G>C	p.Val343Leu	missense_variant	9/15	5		ENSP00000364159
ANKS6	ENST00000444472.5	c.337G>C	p.Val113Leu	missense_variant	3/9	2		ENSP00000398648
ANKS6	ENST00000634393.1	n.1030G>C		non_coding_transcript_exon_variant	8/15	5

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD3 exomes AF: 0.0000131 AC: 3 AN: 229872 Hom.: 0 AF XY: 0.0000240 AC XY: 3 AN XY: 124798

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 SAS exome AF: 0.000112

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000209 AC: 3 AN: 1434246 Hom.: 0 Cov.: 68 AF XY: 0.00000421 AC XY: 3 AN XY: 712346

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000368

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 34

ExAC AF: 0.0000166 AC: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	4.7
DANN	Benign	0.97
DEOGEN2	Benign	0.013	.;T
Eigen	Benign	-0.73
Eigen_PC	Benign	-0.69
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.68	T;T
M_CAP	Benign	0.029	D
MetaRNN	Benign	0.054	T;T
MetaSVM	Benign	-0.76	T
MutationAssessor	Benign	1.4	.;L
MutationTaster	Benign	1.0	P;P;P;P
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-0.92	N;N
REVEL	Benign	0.024
Sift	Benign	0.36	T;T
Sift4G	Benign	0.57	T;T
Polyphen		0.0070	.;B
Vest4		0.17
MutPred		0.17		.;Loss of sheet (P = 0.0457);
MVP		0.59
MPC		0.11
ClinPred		0.054	T
GERP RS		2.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.032
gMVP		0.19

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

Publications

LitVar

Other links and lift over

dbSNP: rs6415847; hg19: chr9-101533220;