chr16-21233744-A-G

Variant summary

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

The NM_145865.3(ANKS4B):ā€‹c.7A>Gā€‹(p.Thr3Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000211 in 1,613,190 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.000020 ( 0 hom., cov: 32)
Exomes š‘“: 0.000021 ( 0 hom. )

Consequence

ANKS4B
NM_145865.3 missense

Scores

4
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.28
Variant links:
Genes affected
ANKS4B (HGNC:26795): (ankyrin repeat and sterile alpha motif domain containing 4B) Involved in brush border assembly; cellular protein-containing complex assembly; and protein localization to microvillus. Located in brush border and microvillus. [provided by Alliance of Genome Resources, Apr 2022]

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=0.2559854).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ANKS4BNM_145865.3 linkuse as main transcriptc.7A>G p.Thr3Ala missense_variant 1/2 ENST00000311620.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ANKS4BENST00000311620.7 linkuse as main transcriptc.7A>G p.Thr3Ala missense_variant 1/21 NM_145865.3 P1

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152082
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000242
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:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000402
AC:
1
AN:
248602
Hom.:
0
AF XY:
0.00000741
AC XY:
1
AN XY:
134866
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
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:
0.00000885
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000212
AC:
31
AN:
1461108
Hom.:
0
Cov.:
30
AF XY:
0.0000206
AC XY:
15
AN XY:
726836
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
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:
0.0000279
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
152082
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74290
show subpopulations
Gnomad4 AFR
AF:
0.0000242
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:
0.0000294
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000329
Hom.:
0
Bravo
AF:
0.0000453
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000120
AC:
1

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 GeneticsOct 22, 2021The c.7A>G (p.T3A) alteration is located in exon 1 (coding exon 1) of the ANKS4B gene. This alteration results from a A to G substitution at nucleotide position 7, causing the threonine (T) at amino acid position 3 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
0.34
BayesDel_addAF
Benign
-0.11
T
BayesDel_noAF
Benign
-0.39
CADD
Benign
21
DANN
Uncertain
0.99
DEOGEN2
Benign
0.026
T
Eigen
Benign
0.15
Eigen_PC
Uncertain
0.28
FATHMM_MKL
Uncertain
0.94
D
M_CAP
Benign
0.014
T
MetaRNN
Benign
0.26
T
MetaSVM
Benign
-0.85
T
MutationAssessor
Benign
1.8
L
MutationTaster
Benign
0.82
D
PrimateAI
Uncertain
0.50
T
PROVEAN
Benign
-1.9
N
REVEL
Benign
0.076
Sift
Benign
0.28
T
Sift4G
Benign
0.47
T
Polyphen
0.41
B
Vest4
0.47
MVP
0.72
MPC
0.36
ClinPred
0.37
T
GERP RS
5.3
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.6
Varity_R
0.14
gMVP
0.56

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: rs369821758; hg19: chr16-21245065; API