rs530838661

Variant names:

• chr6-89612329-G-A
• rs530838661
• NM_001242809.2:c.475G>A

Variant summary

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

The NM_001242809.2(ANKRD6):​c.475G>A​(p.Val159Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000121 in 1,565,848 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000011 (0 hom.)
• Consequence: ANKRD6 NM_001242809.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.38
• Publications: 1 publications found

Genes affected

ANKRD6 (HGNC:17280): (ankyrin repeat domain 6) Predicted to be involved in negative regulation of canonical Wnt signaling pathway and positive regulation of JNK cascade. Predicted to act upstream of or within positive regulation of Wnt signaling pathway, planar cell polarity pathway. Located in intracellular membrane-bounded organelle. [provided by Alliance of Genome Resources, Apr 2022]

LYRM2 (HGNC:25229): (LYR motif containing 2)

LOC124901359 (HGNC:):

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=0.10480785).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001242809.2. 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
	ANKRD6	NM_001242809.2	MANE Select	c.475G>A	p.Val159Ile	missense	Exon 6 of 16	NP_001229738.1	Q9Y2G4-2
	ANKRD6	NM_001242811.1		c.475G>A	p.Val159Ile	missense	Exon 6 of 16	NP_001229740.1	Q9Y2G4-2
	ANKRD6	NM_014942.4		c.475G>A	p.Val159Ile	missense	Exon 6 of 16	NP_055757.3	Q9Y2G4-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKRD6	ENST00000339746.9	TSL:1 MANE Select	c.475G>A	p.Val159Ile	missense	Exon 6 of 16	ENSP00000345767.4	Q9Y2G4-2
	ANKRD6	ENST00000447838.6	TSL:1	c.475G>A	p.Val159Ile	missense	Exon 6 of 16	ENSP00000396771.2	Q9Y2G4-3
	ANKRD6	ENST00000369408.9	TSL:1	c.475G>A	p.Val159Ile	missense	Exon 6 of 15	ENSP00000358416.5	Q9Y2G4-1

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152228 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000113 AC: 2 AN: 176318 AF XY: 0.0000107

Gnomad AFR exome AF: 0.000104

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: 0.0000137

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000113 AC: 16 AN: 1413502 Hom.: 0 Cov.: 31 AF XY: 0.00000859 AC XY: 6 AN XY: 698374

African (AFR) AF: 0.0000310 AC: 1 AN: 32306

American (AMR) AF: 0.00 AC: 0 AN: 37704

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25286

East Asian (EAS) AF: 0.00 AC: 0 AN: 37074

South Asian (SAS) AF: 0.0000125 AC: 1 AN: 79984

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50274

Middle Eastern (MID) AF: 0.000175 AC: 1 AN: 5710

European-Non Finnish (NFE) AF: 0.0000110 AC: 12 AN: 1086516

Other (OTH) AF: 0.0000171 AC: 1 AN: 58648

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152346 Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1 AN XY: 74506

African (AFR) AF: 0.00 AC: 0 AN: 41574

American (AMR) AF: 0.00 AC: 0 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68032

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000264

ExAC AF: 0.0000340 AC: 4

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.066
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	10
DANN	Uncertain	0.97
DEOGEN2	Benign	0.0030	T
Eigen	Benign	-0.51
Eigen_PC	Benign	-0.39
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.0093	T
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.39	N
PhyloP100		1.4
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-0.42	N
REVEL	Benign	0.018
Sift	Benign	0.66	T
Sift4G	Benign	0.36	T
Polyphen		0.029	B
Vest4		0.25
MutPred		0.39		Loss of helix (P = 0.1299)
MVP		0.47
MPC		0.046
ClinPred		0.056	T
GERP RS		2.9
Varity_R		0.018
gMVP		0.14
Mutation Taster		=96/4	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: rs530838661; hg19: chr6-90322048;