chr1-108830574-C-A

Variant summary

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

The NM_152763.5(AKNAD1):​c.1823G>T​(p.Arg608Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000062 in 1,613,896 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

AKNAD1
NM_152763.5 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.546
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=0.05389926).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
AKNAD1NM_152763.5 linkuse as main transcriptc.1823G>T p.Arg608Leu missense_variant 10/16 ENST00000370001.8
LOC105378891XR_947687.3 linkuse as main transcriptn.123-3616C>A intron_variant, non_coding_transcript_variant
AKNAD1NR_049760.2 linkuse as main transcriptn.2035G>T non_coding_transcript_exon_variant 9/14
LOC105378891XR_007066273.1 linkuse as main transcriptn.148-3616C>A intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
AKNAD1ENST00000370001.8 linkuse as main transcriptc.1823G>T p.Arg608Leu missense_variant 10/161 NM_152763.5 P2Q5T1N1-1

Frequencies

GnomAD3 genomes
AF:
0.0000329
AC:
5
AN:
152164
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
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:
0.0000735
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000119
AC:
3
AN:
251184
Hom.:
0
AF XY:
0.0000147
AC XY:
2
AN XY:
135770
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:
0.0000264
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000342
AC:
5
AN:
1461732
Hom.:
0
Cov.:
31
AF XY:
0.00000275
AC XY:
2
AN XY:
727172
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:
0.00000450
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000329
AC:
5
AN:
152164
Hom.:
0
Cov.:
32
AF XY:
0.0000538
AC XY:
4
AN XY:
74344
show subpopulations
Gnomad4 AFR
AF:
0.00
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:
0.0000735
Gnomad4 OTH
AF:
0.00
ExAC
AF:
0.00000824
AC:
1
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

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 18, 2021The c.1823G>T (p.R608L) alteration is located in exon 10 (coding exon 9) of the AKNAD1 gene. This alteration results from a G to T substitution at nucleotide position 1823, causing the arginine (R) at amino acid position 608 to be replaced by a leucine (L). 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
0.15
BayesDel_addAF
Benign
-0.44
T
BayesDel_noAF
Benign
-0.76
CADD
Benign
2.7
DANN
Benign
0.95
DEOGEN2
Benign
0.0038
T;.;.
Eigen
Benign
-1.1
Eigen_PC
Benign
-1.1
FATHMM_MKL
Benign
0.0047
N
LIST_S2
Benign
0.70
T;T;T
M_CAP
Benign
0.0050
T
MetaRNN
Benign
0.054
T;T;T
MetaSVM
Benign
-0.97
T
MutationAssessor
Benign
0.20
N;.;N
MutationTaster
Benign
1.0
N;N;N;N
PrimateAI
Benign
0.18
T
PROVEAN
Benign
0.24
N;N;N
REVEL
Benign
0.0050
Sift
Benign
0.40
T;T;T
Sift4G
Benign
0.26
T;T;T
Polyphen
0.0010
B;.;.
Vest4
0.18
MVP
0.076
MPC
0.029
ClinPred
0.039
T
GERP RS
-2.1
Varity_R
0.081
gMVP
0.058

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.15
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: rs143433407; hg19: chr1-109373196; API