chr1-108823433-G-A

Variant summary

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

The NM_152763.5(AKNAD1):​c.2104C>T​(p.His702Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,848 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: not found (cov: 32)
Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

AKNAD1
NM_152763.5 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.855
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=0.0436472).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
AKNAD1NM_152763.5 linkuse as main transcriptc.2104C>T p.His702Tyr missense_variant 13/16 ENST00000370001.8
LOC105378891XR_947687.3 linkuse as main transcriptn.54-217G>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.2104C>T p.His702Tyr missense_variant 13/161 NM_152763.5 P2Q5T1N1-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000795
AC:
2
AN:
251470
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135908
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:
0.0000176
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000274
AC:
4
AN:
1461848
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
727228
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:
0.00000360
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
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 GeneticsSep 17, 2021The c.2104C>T (p.H702Y) alteration is located in exon 13 (coding exon 12) of the AKNAD1 gene. This alteration results from a C to T substitution at nucleotide position 2104, causing the histidine (H) at amino acid position 702 to be replaced by a tyrosine (Y). 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
0.071
BayesDel_addAF
Benign
-0.27
T
BayesDel_noAF
Benign
-0.61
CADD
Benign
10
DANN
Benign
0.72
DEOGEN2
Benign
0.0055
T;.;.
Eigen
Benign
-0.79
Eigen_PC
Benign
-0.80
FATHMM_MKL
Benign
0.034
N
LIST_S2
Benign
0.64
T;T;T
M_CAP
Benign
0.0019
T
MetaRNN
Benign
0.044
T;T;T
MetaSVM
Benign
-0.96
T
MutationAssessor
Benign
0.90
L;.;L
MutationTaster
Benign
1.0
N;N;N;N
PrimateAI
Benign
0.35
T
PROVEAN
Benign
-1.3
N;N;N
REVEL
Benign
0.087
Sift
Benign
0.30
T;T;T
Sift4G
Benign
0.42
T;T;T
Polyphen
0.0020
B;.;.
Vest4
0.18
MutPred
0.27
Gain of loop (P = 0.0045);.;Gain of loop (P = 0.0045);
MVP
0.014
MPC
0.030
ClinPred
0.034
T
GERP RS
0.36
Varity_R
0.061
gMVP
0.038

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.080
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: rs1023388636; hg19: chr1-109366055; COSMIC: COSV104422423; COSMIC: COSV104422423; API