Variant chr1-108834526-T-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_152763.5(AKNAD1):c.1667A>G(p.Tyr556Cys) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000439 in 1,505,254 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. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00054 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00043 ( 1 hom. )

Consequence

AKNAD1
NM_152763.5 missense, splice_region

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.342

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:

AKNAD1 (HGNC:):

AKNAD1 links:

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=0.046153545).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AKNAD1	NM_152763.5 linkuse as main transcript	c.1667A>G	p.Tyr556Cys	missense_variant, splice_region_variant	9/16	ENST00000370001.8	NP_689976.2	Q5T1N1-1
AKNAD1	NR_049760.2 linkuse as main transcript	n.1958+3024A>G		intron_variant
LOC105378891	XR_007066273.1 linkuse as main transcript	n.294+190T>C		intron_variant
LOC105378891	XR_947687.3 linkuse as main transcript	n.269+190T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AKNAD1	ENST00000370001.8 linkuse as main transcript	c.1667A>G	p.Tyr556Cys	missense_variant, splice_region_variant	9/16	1	NM_152763.5	ENSP00000359018.3		Q5T1N1-1

Frequencies

GnomAD3 genomes

AF:

0.000542

AC:

AN:

60844

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000258

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:

0.00102

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000387

AC:

AN:

131656

Hom.:

AF XY:

0.000324

AC XY:

AN XY:

71092

show subpopulations

Gnomad AFR exome

AF:

0.000221

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:

0.000806

Gnomad OTH exome

AF:

0.000598

GnomAD4 exome

AF:

0.000435

AC:

628

AN:

1444410

Hom.:

Cov.:

AF XY:

0.000406

AC XY:

291

AN XY:

717294

show subpopulations

Gnomad4 AFR exome

AF:

0.0000908

Gnomad4 AMR exome

AF:

0.0000235

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000359

Gnomad4 FIN exome

AF:

0.0000199

Gnomad4 NFE exome

AF:

0.000545

Gnomad4 OTH exome

AF:

0.000301

GnomAD4 genome

AF:

0.000542

AC:

AN:

60844

Hom.:

Cov.:

AF XY:

0.000605

AC XY:

AN XY:

28116

show subpopulations

Gnomad4 AFR

AF:

0.000258

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:

0.00102

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000386

Hom.:

Bravo

AF:

0.000261

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.000183

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

May 28, 2024

The c.1667A>G (p.Y556C) alteration is located in exon 9 (coding exon 8) of the AKNAD1 gene. This alteration results from a A to G substitution at nucleotide position 1667, causing the tyrosine (Y) at amino acid position 556 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

0.10

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.54

CADD

Benign

8.7

DANN

Benign

0.64

DEOGEN2

Benign

0.0019

T;.;.

Eigen

Benign

-0.56

Eigen_PC

Benign

-0.72

FATHMM_MKL

Benign

0.051

LIST_S2

Benign

0.67

T;T;T

M_CAP

Benign

0.0031

MetaRNN

Benign

0.046

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.34

N;.;N

PrimateAI

Benign

0.33

PROVEAN

Benign

-1.5

N;N;N

REVEL

Benign

0.078

Sift

Benign

0.12

T;T;T

Sift4G

Benign

0.17

T;T;T

Polyphen

0.92

P;.;.

Vest4

0.40

MVP

0.13

MPC

0.035

ClinPred

0.027

GERP RS

2.1

Varity_R

0.12

gMVP

0.16

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