10-88831953-G-C

Variant summary

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

The NM_144590.3(ANKRD22):ā€‹c.95C>Gā€‹(p.Ala32Gly) variant causes a missense change. The variant allele was found at a frequency of 0.0000242 in 1,613,766 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.000099 ( 0 hom., cov: 32)
Exomes š‘“: 0.000016 ( 0 hom. )

Consequence

ANKRD22
NM_144590.3 missense

Scores

3
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.71
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=0.109736085).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ANKRD22NM_144590.3 linkuse as main transcriptc.95C>G p.Ala32Gly missense_variant 2/6 ENST00000371930.5 NP_653191.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ANKRD22ENST00000371930.5 linkuse as main transcriptc.95C>G p.Ala32Gly missense_variant 2/61 NM_144590.3 ENSP00000360998 P1

Frequencies

GnomAD3 genomes
AF:
0.0000986
AC:
15
AN:
152118
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000362
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000477
AC:
12
AN:
251318
Hom.:
0
AF XY:
0.0000368
AC XY:
5
AN XY:
135834
show subpopulations
Gnomad AFR exome
AF:
0.000615
Gnomad AMR exome
AF:
0.0000579
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:
0.0000164
AC:
24
AN:
1461648
Hom.:
0
Cov.:
30
AF XY:
0.00000963
AC XY:
7
AN XY:
727130
show subpopulations
Gnomad4 AFR exome
AF:
0.000598
Gnomad4 AMR exome
AF:
0.0000448
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:
0.0000331
GnomAD4 genome
AF:
0.0000986
AC:
15
AN:
152118
Hom.:
0
Cov.:
32
AF XY:
0.000135
AC XY:
10
AN XY:
74304
show subpopulations
Gnomad4 AFR
AF:
0.000362
Gnomad4 AMR
AF:
0.00
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:
0.0000126
Hom.:
0
Bravo
AF:
0.000162
ESP6500AA
AF:
0.000681
AC:
3
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.0000576
AC:
7

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 GeneticsJan 31, 2024The c.95C>G (p.A32G) alteration is located in exon 2 (coding exon 2) of the ANKRD22 gene. This alteration results from a C to G substitution at nucleotide position 95, causing the alanine (A) at amino acid position 32 to be replaced by a glycine (G). 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
0.19
BayesDel_addAF
Benign
-0.40
T
BayesDel_noAF
Benign
-0.45
CADD
Benign
17
DANN
Benign
0.96
DEOGEN2
Benign
0.022
T
Eigen
Benign
-0.54
Eigen_PC
Benign
-0.50
FATHMM_MKL
Benign
0.59
D
LIST_S2
Benign
0.73
T
M_CAP
Benign
0.077
D
MetaRNN
Benign
0.11
T
MetaSVM
Benign
-0.77
T
MutationAssessor
Benign
1.2
L
MutationTaster
Benign
1.0
N
PrimateAI
Benign
0.28
T
PROVEAN
Uncertain
-2.7
D
REVEL
Benign
0.22
Sift
Uncertain
0.0040
D
Sift4G
Uncertain
0.011
D
Polyphen
0.065
B
Vest4
0.23
MVP
0.79
MPC
0.18
ClinPred
0.078
T
GERP RS
4.2
Varity_R
0.25
gMVP
0.38

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: rs146755980; hg19: chr10-90591710; API