rs6415847

Variant names:

• chr9-98770938-C-T
• rs6415847
• NM_173551.5:c.1930G>A

Your query was ambiguous. Multiple possible variants found:

• chr9-98770938-C-T
• chr9-98770938-C-G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_173551.5(ANKS6):​c.1930G>A​(p.Val644Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.952 in 1,586,358 control chromosomes in the GnomAD database, including 720,902 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.94 (68030 hom., cov: 34)
  • Exomes 𝑓: 0.95 (652872 hom.)
• Consequence: ANKS6 NM_173551.5 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 1.31
• Publications: 29 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=6.176339E-7).
• BP6: Variant 9-98770938-C-T is Benign according to our data. Variant chr9-98770938-C-T is described in ClinVar as Benign. ClinVar VariationId is 262847.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.96 is higher than 0.05.

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.1930G>A	p.Val644Ile	missense	Exon 10 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.1930G>A	p.Val644Ile	missense	Exon 10 of 15	ENSP00000297837.6	Q68DC2-1
	ANKS6	ENST00000375019.6	TSL:5	c.1027G>A	p.Val343Ile	missense	Exon 9 of 15	ENSP00000364159.2	A0A0A0MRS7
	ANKS6	ENST00000444472.5	TSL:2	c.334G>A	p.Val112Ile	missense	Exon 3 of 9	ENSP00000398648.1	H7C163

Frequencies

GnomAD3 genomes AF: 0.944 AC: 143596 AN: 152180 Hom.: 67989 Cov.: 34

Gnomad AFR AF: 0.953

Gnomad AMI AF: 0.999

Gnomad AMR AF: 0.882

Gnomad ASJ AF: 0.948

Gnomad EAS AF: 0.719

Gnomad SAS AF: 0.868

Gnomad FIN AF: 0.990

Gnomad MID AF: 0.946

Gnomad NFE AF: 0.966

Gnomad OTH AF: 0.942

GnomAD2 exomes AF: 0.919 AC: 211326 AN: 229872 AF XY: 0.924

Gnomad AFR exome AF: 0.953

Gnomad AMR exome AF: 0.800

Gnomad ASJ exome AF: 0.951

Gnomad EAS exome AF: 0.718

Gnomad FIN exome AF: 0.992

Gnomad NFE exome AF: 0.968

Gnomad OTH exome AF: 0.943

GnomAD4 exome AF: 0.953 AC: 1366317 AN: 1434060 Hom.: 652872 Cov.: 68 AF XY: 0.952 AC XY: 677690 AN XY: 712228

African (AFR) AF: 0.956 AC: 31018 AN: 32446

American (AMR) AF: 0.813 AC: 33528 AN: 41224

Ashkenazi Jewish (ASJ) AF: 0.948 AC: 24113 AN: 25438

East Asian (EAS) AF: 0.733 AC: 27696 AN: 37790

South Asian (SAS) AF: 0.885 AC: 72072 AN: 81394

European-Finnish (FIN) AF: 0.992 AC: 52598 AN: 53036

Middle Eastern (MID) AF: 0.954 AC: 5414 AN: 5674

European-Non Finnish (NFE) AF: 0.969 AC: 1063849 AN: 1097888

Other (OTH) AF: 0.947 AC: 56029 AN: 59170

GnomAD4 genome AF: 0.943 AC: 143690 AN: 152298 Hom.: 68030 Cov.: 34 AF XY: 0.941 AC XY: 70062 AN XY: 74458

African (AFR) AF: 0.953 AC: 39593 AN: 41562

American (AMR) AF: 0.881 AC: 13489 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.948 AC: 3290 AN: 3472

East Asian (EAS) AF: 0.719 AC: 3708 AN: 5156

South Asian (SAS) AF: 0.868 AC: 4190 AN: 4826

European-Finnish (FIN) AF: 0.990 AC: 10518 AN: 10622

Middle Eastern (MID) AF: 0.942 AC: 277 AN: 294

European-Non Finnish (NFE) AF: 0.966 AC: 65728 AN: 68036

Other (OTH) AF: 0.940 AC: 1986 AN: 2112

Alfa AF: 0.952 Hom.: 226975

Bravo AF: 0.934

TwinsUK AF: 0.965 AC: 3577

ALSPAC AF: 0.964 AC: 3717

ESP6500AA AF: 0.955 AC: 3644

ESP6500EA AF: 0.967 AC: 7978

ExAC AF: 0.921 AC: 111266

Asia WGS AF: 0.828 AC: 2878 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	Nephronophthisis 16 (2)
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.079
BayesDel_addAF	Benign	-0.59	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	2.4
DANN	Benign	0.82
DEOGEN2	Benign	0.0075	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.89
FATHMM_MKL	Benign	0.053	N
LIST_S2	Benign	0.47	T
MetaRNN	Benign	6.2e-7	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.035	N
PhyloP100		1.3
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.020	N
REVEL	Benign	0.070
Sift	Benign	1.0	T
Sift4G	Benign	0.36	T
Polyphen		0.0	B
Vest4		0.031
MPC		0.082
ClinPred		0.00073	T
GERP RS		2.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.017
gMVP		0.11
Mutation Taster		=99/1	polymorphism (auto)

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: rs6415847; hg19: chr9-101533220; COSMIC: COSV62050816;