Genetic Variant AKNAD1:p.Ala638Pro (chr1-108827229-C-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_152763.5(AKNAD1):c.1912G>C(p.Ala638Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,842 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A638T) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

AKNAD1
NM_152763.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0630

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:

LOC105378891 (HGNC:):

LOC105378891 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.052082986).

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.1912G>C	p.Ala638Pro	missense	Exon 11 of 16	NP_689976.2	Q5T1N1-1
	AKNAD1	NR_049760.2		n.2124G>C		non_coding_transcript_exon	Exon 10 of 14

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
AKNAD1	ENST00000370001.8	TSL:1 MANE Select	c.1912G>C	p.Ala638Pro	missense	Exon 11 of 16	ENSP00000359018.3	Q5T1N1-1
AKNAD1	ENST00000369995.7	TSL:5	c.1912G>C	p.Ala638Pro	missense	Exon 11 of 14	ENSP00000359012.3	Q5T1N1-4
AKNAD1	ENST00000369994.5	TSL:5	c.1822G>C	p.Ala608Pro	missense	Exon 10 of 13	ENSP00000359011.1	Q5T1N2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1459842

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726244

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

33462

American (AMR)

AF:

0.00

AC:

AN:

44566

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26088

East Asian (EAS)

AF:

0.00

AC:

AN:

39070

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86034

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53412

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5648

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111286

Other (OTH)

AF:

0.00

AC:

AN:

60276

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.275

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.72

CADD

Benign

2.4

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.0043

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.029

LIST_S2

Benign

0.50

M_CAP

Benign

0.0048

MetaRNN

Benign

0.052

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.97

PhyloP100

-0.063

PrimateAI

Benign

0.22

PROVEAN

Benign

-1.5

REVEL

Benign

0.028

Sift

Benign

0.13

Sift4G

Benign

0.21

Polyphen

0.011

Vest4

0.074

MutPred

0.17

Gain of disorder (P = 0.0287)

MVP

0.040

MPC

0.031

ClinPred

0.090

GERP RS

0.99

Varity_R

0.099

gMVP

0.041

Mutation Taster

=95/5

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over