Variant 1-108835031-G-A 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.1562C>T(p.Pro521Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000141 in 1,420,444 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: 0.0000014 ( 0 hom. )

Consequence

AKNAD1
NM_152763.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0360

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:

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=0.045084625).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
AKNAD1	NM_152763.5 linkuse as main transcript	c.1562C>T	p.Pro521Leu	missense_variant	8/16	ENST00000370001.8
LOC105378891	XR_947687.3 linkuse as main transcript	n.269+695G>A		intron_variant, non_coding_transcript_variant
AKNAD1	NR_049760.2 linkuse as main transcript	n.1958+2519C>T		intron_variant, non_coding_transcript_variant
LOC105378891	XR_007066273.1 linkuse as main transcript	n.294+695G>A		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.1562C>T	p.Pro521Leu	missense_variant	8/16	1	NM_152763.5	P2	Q5T1N1-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000482

AC:

AN:

207478

Hom.:

AF XY:

0.00

AC XY:

AN XY:

114344

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:

0.0000477

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000141

AC:

AN:

1420444

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

706810

show subpopulations

Gnomad4 AFR exome

AF:

0.0000336

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:

0.0000188

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Jan 03, 2024

The c.1562C>T (p.P521L) alteration is located in exon 8 (coding exon 7) of the AKNAD1 gene. This alteration results from a C to T substitution at nucleotide position 1562, causing the proline (P) at amino acid position 521 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

0.072

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.73

Cadd

Benign

1.5

Dann

Benign

0.33

DEOGEN2

Benign

0.0010

T;.

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.017

LIST_S2

Benign

0.51

T;T

M_CAP

Benign

0.0032

MetaRNN

Benign

0.045

T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

-0.20

N;N

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Benign

0.25

PROVEAN

Benign

0.68

N;N

REVEL

Benign

0.0090

Sift

Benign

0.28

T;T

Sift4G

Benign

0.35

T;T

Polyphen

0.0010

B;.

Vest4

0.17

MutPred

0.17

Gain of helix (P = 0.0425);Gain of helix (P = 0.0425);

MVP

0.092

MPC

0.026

ClinPred

0.032

GERP RS

-0.66

Varity_R

0.024

gMVP

0.061

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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