Variant chr1-108817057-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.2370A>G(p.Ile790Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000116 in 1,461,718 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: 31)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

AKNAD1
NM_152763.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.94

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 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=0.01857698).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
AKNAD1	NM_152763.5 linkuse as main transcript	c.2370A>G	p.Ile790Met	missense_variant	15/16	ENST00000370001.8
LOC105378891	XR_947687.3 linkuse as main transcript	n.53+3415T>C		intron_variant, non_coding_transcript_variant
AKNAD1	NR_049760.2 linkuse as main transcript	n.2500A>G		non_coding_transcript_exon_variant	13/14
LOC105378891	XR_007066280.1 linkuse as main transcript	n.53+3415T>C		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.2370A>G	p.Ile790Met	missense_variant	15/16	1	NM_152763.5	P2	Q5T1N1-1
AKNAD1	ENST00000466413.1 linkuse as main transcript	n.398A>G		non_coding_transcript_exon_variant	1/2	2
AKNAD1	ENST00000477908.1 linkuse as main transcript	n.155A>G		non_coding_transcript_exon_variant	2/3	3
AKNAD1	ENST00000474186.5 linkuse as main transcript	c.*119A>G		3_prime_UTR_variant, NMD_transcript_variant	13/14	2			Q5T1N1-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000159

AC:

AN:

251248

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135800

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000218

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000116

AC:

AN:

1461718

Hom.:

Cov.:

AF XY:

0.0000110

AC XY:

AN XY:

727158

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.000232

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000302

ExAC

AF:

0.0000247

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 23, 2022

The c.2370A>G (p.I790M) alteration is located in exon 15 (coding exon 14) of the AKNAD1 gene. This alteration results from a A to G substitution at nucleotide position 2370, causing the isoleucine (I) at amino acid position 790 to be replaced by a methionine (M). 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

0.059

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.15

DANN

Benign

0.25

DEOGEN2

Benign

0.0013

Eigen

Benign

-2.0

Eigen_PC

Benign

-2.1

FATHMM_MKL

Benign

0.013

LIST_S2

Benign

0.28

M_CAP

Benign

0.0033

MetaRNN

Benign

0.019

MetaSVM

Benign

-0.96

MutationAssessor

Benign

-0.34

MutationTaster

Benign

1.0

PrimateAI

Benign

0.33

PROVEAN

Benign

0.13

REVEL

Benign

0.019

Sift

Benign

0.42

Sift4G

Benign

0.18

Polyphen

0.0

Vest4

0.067

MutPred

0.21

Loss of catalytic residue at L795 (P = 0.0447);

MVP

0.014

MPC

0.026

ClinPred

0.035

GERP RS

-11

Varity_R

0.051

gMVP

0.029

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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