Variant chr1-108835055-A-G 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.1538T>C(p.Ile513Thr) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000704 in 1,421,428 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.0e-7 ( 0 hom. )

Consequence

AKNAD1
NM_152763.5 missense, splice_region

Scores

Splicing: ADA: 0.009619

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.577

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=0.041939914).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
AKNAD1	NM_152763.5 linkuse as main transcript	c.1538T>C	p.Ile513Thr	missense_variant, splice_region_variant	8/16	ENST00000370001.8
LOC105378891	XR_947687.3 linkuse as main transcript	n.269+719A>G		intron_variant, non_coding_transcript_variant
AKNAD1	NR_049760.2 linkuse as main transcript	n.1958+2495T>C		intron_variant, non_coding_transcript_variant
LOC105378891	XR_007066273.1 linkuse as main transcript	n.294+719A>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.1538T>C	p.Ile513Thr	missense_variant, splice_region_variant	8/16	1	NM_152763.5	P2	Q5T1N1-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.04e-7

AC:

AN:

1421428

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

707282

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:

9.11e-7

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

Dec 14, 2023

The c.1538T>C (p.I513T) alteration is located in exon 8 (coding exon 7) of the AKNAD1 gene. This alteration results from a T to C substitution at nucleotide position 1538, causing the isoleucine (I) at amino acid position 513 to be replaced by a threonine (T). 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

0.22

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.67

CADD

Benign

5.5

DANN

Benign

0.88

DEOGEN2

Benign

0.0031

T;.

Eigen

Benign

-0.89

Eigen_PC

Benign

-0.91

FATHMM_MKL

Benign

0.070

LIST_S2

Benign

0.50

T;T

M_CAP

Benign

0.0025

MetaRNN

Benign

0.042

T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.34

N;N

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Benign

0.38

PROVEAN

Benign

0.40

N;N

REVEL

Benign

0.057

Sift

Benign

0.15

T;T

Sift4G

Benign

0.19

T;T

Polyphen

0.084

B;.

Vest4

0.14

MutPred

0.28

Loss of stability (P = 0.0076);Loss of stability (P = 0.0076);

MVP

0.040

MPC

0.030

ClinPred

0.14

GERP RS

3.2

Varity_R

0.047

gMVP

0.042

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0096

dbscSNV1_RF

Benign

0.084

SpliceAI score (max)

0.12

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over