Genetic Variant AKNAD1:p.Pro540Thr (chr1-108834975-G-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_152763.5(AKNAD1):c.1618C>A(p.Pro540Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P540Q) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

AKNAD1
NM_152763.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.646

Publications

0 publications found

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:

ENSG00000307428 (HGNC:):

ENSG00000307428 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.075926214).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152763.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AKNAD1	NM_152763.5	MANE Select	c.1618C>A	p.Pro540Thr	missense	Exon 8 of 16	NP_689976.2	Q5T1N1-1
	AKNAD1	NR_049760.2		n.1958+2575C>A		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
AKNAD1	ENST00000370001.8	TSL:1 MANE Select	c.1618C>A	p.Pro540Thr	missense	Exon 8 of 16	ENSP00000359018.3	Q5T1N1-1
AKNAD1	ENST00000369995.7	TSL:5	c.1618C>A	p.Pro540Thr	missense	Exon 8 of 14	ENSP00000359012.3	Q5T1N1-4
AKNAD1	ENST00000369994.5	TSL:5	c.1537-9C>A		intron	N/A	ENSP00000359011.1	Q5T1N2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1402608

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

697304

African (AFR)

AF:

0.00

AC:

AN:

28584

American (AMR)

AF:

0.00

AC:

AN:

28934

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23538

East Asian (EAS)

AF:

0.00

AC:

AN:

35460

South Asian (SAS)

AF:

0.00

AC:

AN:

78216

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52994

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5500

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1091690

Other (OTH)

AF:

0.00

AC:

AN:

57692

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.077

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.11

(source)

DANN

Benign

0.89

DEOGEN2

Benign

0.0048

Eigen

Benign

-0.93

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.010

LIST_S2

Benign

0.56

M_CAP

Benign

0.014

MetaRNN

Benign

0.076

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.90

PhyloP100

-0.65

PrimateAI

Benign

0.25

PROVEAN

Benign

-0.85

REVEL

Benign

0.0060

Sift

Benign

0.088

Sift4G

Benign

0.11

Polyphen

0.0

Vest4

0.093

MutPred

0.27

Gain of glycosylation at P540 (P = 0.0112)

MVP

0.040

MPC

0.027

ClinPred

0.13

GERP RS

-1.1

Varity_R

0.034

gMVP

0.12

Mutation Taster

=97/3

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over