Menu
GeneBe

6-89606057-A-G

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_001242809.2(ANKRD6):c.369A>G(p.Ser123=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00108 in 1,595,724 control chromosomes in the GnomAD database, including 18 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0058 ( 11 hom., cov: 32)
Exomes 𝑓: 0.00058 ( 7 hom. )

Consequence

ANKRD6
NM_001242809.2 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0620
Variant links:
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)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.69).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 6-89606057-A-G is Benign according to our data. Variant chr6-89606057-A-G is described in ClinVar as [Benign]. Clinvar id is 784092.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-0.062 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00579 (881/152290) while in subpopulation AFR AF= 0.0204 (847/41556). AF 95% confidence interval is 0.0192. There are 11 homozygotes in gnomad4. There are 422 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 11 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ANKRD6NM_001242809.2 linkuse as main transcriptc.369A>G p.Ser123= synonymous_variant 5/16 ENST00000339746.9
LOC124901359XR_007059673.1 linkuse as main transcriptn.206-126T>C intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ANKRD6ENST00000339746.9 linkuse as main transcriptc.369A>G p.Ser123= synonymous_variant 5/161 NM_001242809.2 A1Q9Y2G4-2

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00579
AC:
881
AN:
152172
Hom.:
11
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0204
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00157
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:
0.0000147
Gnomad OTH
AF:
0.00430
GnomAD3 exomes
AF:
0.00144
AC:
321
AN:
222358
Hom.:
3
AF XY:
0.00113
AC XY:
135
AN XY:
119514
show subpopulations
Gnomad AFR exome
AF:
0.0218
Gnomad AMR exome
AF:
0.000726
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000120
Gnomad OTH exome
AF:
0.000181
GnomAD4 exome
AF:
0.000583
AC:
842
AN:
1443434
Hom.:
7
Cov.:
28
AF XY:
0.000492
AC XY:
352
AN XY:
715978
show subpopulations
Gnomad4 AFR exome
AF:
0.0215
Gnomad4 AMR exome
AF:
0.00101
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000290
Gnomad4 OTH exome
AF:
0.000821
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00579
AC:
881
AN:
152290
Hom.:
11
Cov.:
32
AF XY:
0.00567
AC XY:
422
AN XY:
74470
show subpopulations
Gnomad4 AFR
AF:
0.0204
Gnomad4 AMR
AF:
0.00157
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00426
Alfa
AF:
0.00313
Hom.:
2
Bravo
AF:
0.00696
Asia WGS
AF:
0.000577
AC:
2
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeMay 21, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.69
Cadd
Benign
5.9
Dann
Benign
0.69

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs61744890; hg19: chr6-90315776; API