chr1-108837569-A-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_152763.5(AKNAD1):ā€‹c.1517T>Gā€‹(p.Phe506Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000126 in 1,613,984 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.000072 ( 0 hom., cov: 32)
Exomes š‘“: 0.00013 ( 1 hom. )

Consequence

AKNAD1
NM_152763.5 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.955
Variant links:
Genes affected
AKNAD1 (HGNC:28398): (AKNA domain containing 1) This gene encodes a protein which contains a domain found in an AT-hook-containing transcription factor. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2012]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.0533987).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
AKNAD1NM_152763.5 linkuse as main transcriptc.1517T>G p.Phe506Cys missense_variant 7/16 ENST00000370001.8
AKNAD1NR_049760.2 linkuse as main transcriptn.1939T>G non_coding_transcript_exon_variant 8/14

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
AKNAD1ENST00000370001.8 linkuse as main transcriptc.1517T>G p.Phe506Cys missense_variant 7/161 NM_152763.5 P2Q5T1N1-1

Frequencies

GnomAD3 genomes
AF:
0.0000723
AC:
11
AN:
152178
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000483
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:
0.000118
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.0000955
AC:
24
AN:
251406
Hom.:
1
AF XY:
0.000125
AC XY:
17
AN XY:
135874
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000868
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:
0.000185
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000131
AC:
192
AN:
1461806
Hom.:
1
Cov.:
31
AF XY:
0.000124
AC XY:
90
AN XY:
727198
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.0000447
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:
0.000160
Gnomad4 OTH exome
AF:
0.000182
GnomAD4 genome
AF:
0.0000723
AC:
11
AN:
152178
Hom.:
0
Cov.:
32
AF XY:
0.0000673
AC XY:
5
AN XY:
74336
show subpopulations
Gnomad4 AFR
AF:
0.0000483
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:
0.000118
Gnomad4 OTH
AF:
0.000478
Alfa
AF:
0.000154
Hom.:
0
Bravo
AF:
0.0000756
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000349
AC:
3
ExAC
AF:
0.0000824
AC:
10
EpiCase
AF:
0.000218
EpiControl
AF:
0.000237

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 26, 2022The c.1517T>G (p.F506C) alteration is located in exon 7 (coding exon 6) of the AKNAD1 gene. This alteration results from a T to G substitution at nucleotide position 1517, causing the phenylalanine (F) at amino acid position 506 to be replaced by a cysteine (C). 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
0.085
BayesDel_addAF
Benign
-0.51
T
BayesDel_noAF
Benign
-0.70
CADD
Benign
10
DANN
Benign
0.43
DEOGEN2
Benign
0.0012
T;.;.
Eigen
Benign
-1.1
Eigen_PC
Benign
-1.1
FATHMM_MKL
Benign
0.045
N
LIST_S2
Benign
0.32
T;T;T
M_CAP
Benign
0.0062
T
MetaRNN
Benign
0.053
T;T;T
MetaSVM
Benign
-0.96
T
MutationAssessor
Benign
0.0
N;.;N
MutationTaster
Benign
1.0
N;N;N;N
PrimateAI
Benign
0.30
T
PROVEAN
Benign
0.29
N;N;N
REVEL
Benign
0.034
Sift
Benign
0.037
D;T;D
Sift4G
Benign
0.085
T;T;T
Polyphen
0.0010
B;.;.
Vest4
0.12
MVP
0.11
MPC
0.045
ClinPred
0.027
T
GERP RS
1.1
Varity_R
0.058
gMVP
0.072

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: rs370267672; hg19: chr1-109380191; API