chr1-1419135-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001145210.3(ANKRD65):ā€‹c.1165G>Cā€‹(p.Glu389Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.127 in 1,529,968 control chromosomes in the GnomAD database, including 29,030 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: š‘“ 0.28 ( 12296 hom., cov: 33)
Exomes š‘“: 0.11 ( 16734 hom. )

Consequence

ANKRD65
NM_001145210.3 missense

Scores

18

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.244
Variant links:
Genes affected
ANKRD65 (HGNC:42950): (ankyrin repeat domain 65)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=1.624828E-6).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.732 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ANKRD65NM_001145210.3 linkuse as main transcriptc.1165G>C p.Glu389Gln missense_variant 4/4 ENST00000537107.6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ANKRD65ENST00000537107.6 linkuse as main transcriptc.1165G>C p.Glu389Gln missense_variant 4/45 NM_001145210.3 P1E5RJM6-1

Frequencies

GnomAD3 genomes
AF:
0.282
AC:
42897
AN:
152026
Hom.:
12242
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.738
Gnomad AMI
AF:
0.127
Gnomad AMR
AF:
0.201
Gnomad ASJ
AF:
0.115
Gnomad EAS
AF:
0.116
Gnomad SAS
AF:
0.162
Gnomad FIN
AF:
0.149
Gnomad MID
AF:
0.184
Gnomad NFE
AF:
0.0775
Gnomad OTH
AF:
0.243
GnomAD3 exomes
AF:
0.168
AC:
23561
AN:
140298
Hom.:
3619
AF XY:
0.156
AC XY:
11697
AN XY:
74836
show subpopulations
Gnomad AFR exome
AF:
0.765
Gnomad AMR exome
AF:
0.253
Gnomad ASJ exome
AF:
0.105
Gnomad EAS exome
AF:
0.0991
Gnomad SAS exome
AF:
0.164
Gnomad FIN exome
AF:
0.155
Gnomad NFE exome
AF:
0.0803
Gnomad OTH exome
AF:
0.137
GnomAD4 exome
AF:
0.110
AC:
151615
AN:
1377824
Hom.:
16734
Cov.:
31
AF XY:
0.110
AC XY:
74056
AN XY:
675950
show subpopulations
Gnomad4 AFR exome
AF:
0.768
Gnomad4 AMR exome
AF:
0.242
Gnomad4 ASJ exome
AF:
0.107
Gnomad4 EAS exome
AF:
0.137
Gnomad4 SAS exome
AF:
0.166
Gnomad4 FIN exome
AF:
0.151
Gnomad4 NFE exome
AF:
0.0776
Gnomad4 OTH exome
AF:
0.145
GnomAD4 genome
AF:
0.283
AC:
43017
AN:
152144
Hom.:
12296
Cov.:
33
AF XY:
0.281
AC XY:
20920
AN XY:
74396
show subpopulations
Gnomad4 AFR
AF:
0.739
Gnomad4 AMR
AF:
0.200
Gnomad4 ASJ
AF:
0.115
Gnomad4 EAS
AF:
0.116
Gnomad4 SAS
AF:
0.162
Gnomad4 FIN
AF:
0.149
Gnomad4 NFE
AF:
0.0776
Gnomad4 OTH
AF:
0.243
Alfa
AF:
0.157
Hom.:
987
Bravo
AF:
0.307
TwinsUK
AF:
0.0744
AC:
276
ALSPAC
AF:
0.0781
AC:
301
ExAC
AF:
0.150
AC:
3250
Asia WGS
AF:
0.211
AC:
731
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.070
BayesDel_addAF
Benign
-0.61
T
BayesDel_noAF
Benign
-0.51
CADD
Benign
0.26
DANN
Benign
0.53
DEOGEN2
Benign
0.0016
T;T
Eigen
Benign
-1.4
Eigen_PC
Benign
-1.5
FATHMM_MKL
Benign
0.0019
N
LIST_S2
Benign
0.21
T;.
MetaRNN
Benign
0.0000016
T;T
MetaSVM
Benign
-0.97
T
MutationAssessor
Benign
0.0
N;N
MutationTaster
Benign
1.0
P;P;P
PrimateAI
Benign
0.37
T
PROVEAN
Benign
0.63
N;.
REVEL
Benign
0.067
Sift
Benign
1.0
T;.
Sift4G
Benign
1.0
T;T
Polyphen
0.0
B;B
Vest4
0.060
ClinPred
0.000014
T
GERP RS
0.25
Varity_R
0.038
gMVP
0.27

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: rs904589; hg19: chr1-1354515; COSMIC: COSV70987108; COSMIC: COSV70987108; API