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GeneBe

10-88826114-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_144590.3(ANKRD22):c.323T>C(p.Val108Ala) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.0000418 in 1,604,708 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000098 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000036 ( 0 hom. )

Consequence

ANKRD22
NM_144590.3 missense, splice_region

Scores

3
16
Splicing: ADA: 0.1357
2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.86
Variant links:
Genes affected
ANKRD22 (HGNC:28321): (ankyrin repeat domain 22)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.15019977).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ANKRD22NM_144590.3 linkuse as main transcriptc.323T>C p.Val108Ala missense_variant, splice_region_variant 4/6 ENST00000371930.5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ANKRD22ENST00000371930.5 linkuse as main transcriptc.323T>C p.Val108Ala missense_variant, splice_region_variant 4/61 NM_144590.3 P1

Frequencies

GnomAD3 genomes
AF:
0.0000986
AC:
15
AN:
152200
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000982
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000163
AC:
40
AN:
244930
Hom.:
0
AF XY:
0.000128
AC XY:
17
AN XY:
132358
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00121
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:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000358
AC:
52
AN:
1452390
Hom.:
0
Cov.:
30
AF XY:
0.0000249
AC XY:
18
AN XY:
722646
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00118
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:
0.00
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.0000985
AC:
15
AN:
152318
Hom.:
0
Cov.:
32
AF XY:
0.000134
AC XY:
10
AN XY:
74494
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.000980
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000676
Hom.:
0
Bravo
AF:
0.000128
ExAC
AF:
0.0000824
AC:
10

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsApr 12, 2022The c.323T>C (p.V108A) alteration is located in exon 4 (coding exon 4) of the ANKRD22 gene. This alteration results from a T to C substitution at nucleotide position 323, causing the valine (V) at amino acid position 108 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.33
BayesDel_addAF
Benign
-0.37
T
BayesDel_noAF
Benign
-0.34
Cadd
Benign
23
Dann
Uncertain
0.99
DEOGEN2
Benign
0.0030
T
Eigen
Benign
0.062
Eigen_PC
Benign
0.20
FATHMM_MKL
Uncertain
0.88
D
LIST_S2
Benign
0.79
T
M_CAP
Benign
0.016
T
MetaRNN
Benign
0.15
T
MetaSVM
Benign
-0.99
T
MutationAssessor
Benign
0.34
N
MutationTaster
Benign
0.93
D
PrimateAI
Uncertain
0.62
T
PROVEAN
Benign
-1.7
N
REVEL
Benign
0.096
Sift
Benign
0.45
T
Sift4G
Benign
0.54
T
Polyphen
0.43
B
Vest4
0.63
MutPred
0.44
Gain of disorder (P = 0.0432);
MVP
0.39
MPC
0.28
ClinPred
0.081
T
GERP RS
5.4
Varity_R
0.12
gMVP
0.41

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.14
dbscSNV1_RF
Benign
0.40
SpliceAI score (max)
0.040
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: rs761733836; hg19: chr10-90585871; API