Variant chr1-108816177-T-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_152763.5(AKNAD1):c.2505A>C(p.Lys835Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000954 in 1,604,424 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00010 ( 0 hom. )

Consequence

AKNAD1
NM_152763.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.673

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]

AKNAD1 links:

LOC105378891 (HGNC:):

LOC105378891 links:

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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=0.1700769).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
AKNAD1	NM_152763.5 linkuse as main transcript	c.2505A>C	p.Lys835Asn	missense_variant	16/16	ENST00000370001.8
LOC105378891	XR_947687.3 linkuse as main transcript	n.53+2535T>G		intron_variant, non_coding_transcript_variant
AKNAD1	NR_049760.2 linkuse as main transcript	n.2635A>C		non_coding_transcript_exon_variant	14/14
LOC105378891	XR_007066280.1 linkuse as main transcript	n.53+2535T>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AKNAD1	ENST00000370001.8 linkuse as main transcript	c.2505A>C	p.Lys835Asn	missense_variant	16/16	1	NM_152763.5	P2	Q5T1N1-1
AKNAD1	ENST00000466413.1 linkuse as main transcript	n.533A>C		non_coding_transcript_exon_variant	2/2	2
AKNAD1	ENST00000477908.1 linkuse as main transcript	n.464A>C		non_coding_transcript_exon_variant	3/3	3
AKNAD1	ENST00000474186.5 linkuse as main transcript	c.*254A>C		3_prime_UTR_variant, NMD_transcript_variant	14/14	2			Q5T1N1-3

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152182

Hom.:

Cov.:

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:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000411

AC:

AN:

243512

Hom.:

AF XY:

0.0000304

AC XY:

AN XY:

131502

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:

0.0000895

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000103

AC:

149

AN:

1452242

Hom.:

Cov.:

AF XY:

0.0000984

AC XY:

AN XY:

721728

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:

0.000124

Gnomad4 OTH exome

AF:

0.000200

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152182

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74358

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:

0.0000588

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000113

Hom.:

Bravo

AF:

0.0000227

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.0000659

AC:

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 submitter

clinical testing

Ambry Genetics

Mar 25, 2024

The c.2505A>C (p.K835N) alteration is located in exon 16 (coding exon 15) of the AKNAD1 gene. This alteration results from a A to C substitution at nucleotide position 2505, causing the lysine (K) at amino acid position 835 to be replaced by an asparagine (N). 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

Uncertain

0.48

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.77

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.0088

Eigen

Benign

-0.29

Eigen_PC

Benign

-0.39

FATHMM_MKL

Benign

0.48

LIST_S2

Benign

0.43

M_CAP

Benign

0.0088

MetaRNN

Benign

0.17

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.0

MutationTaster

Benign

1.0

PrimateAI

Benign

0.46

PROVEAN

Benign

-1.6

REVEL

Benign

0.088

Sift

Uncertain

0.0070

Sift4G

Uncertain

0.028

Polyphen

1.0

Vest4

0.13

MutPred

0.23

Loss of ubiquitination at K835 (P = 0.1306);

MVP

0.030

MPC

0.21

ClinPred

0.20

GERP RS

2.1

Varity_R

0.11

gMVP

0.052

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over