NM_152763.5:c.1823G>A

Variant names:

• chr1-108830574-C-T
• rs143433407
• NM_152763.5:c.1823G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_152763.5(AKNAD1):​c.1823G>A​(p.Arg608His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00113 in 1,614,010 control chromosomes in the GnomAD database, including 21 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 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. R608L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0059 (12 hom., cov: 32)
  • Exomes 𝑓: 0.00063 (9 hom.)
• Consequence: AKNAD1 NM_152763.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.546
• Publications: 2 publications found

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]

LOC105378891 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0034677088).
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00592 (902/152280) while in subpopulation AFR AF = 0.0208 (865/41558). AF 95% confidence interval is 0.0197. There are 12 homozygotes in GnomAd4. There are 434 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 12 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AKNAD1	NM_152763.5	c.1823G>A	p.Arg608His	missense_variant	Exon 10 of 16	ENST00000370001.8	NP_689976.2
AKNAD1	NR_049760.2	n.2035G>A		non_coding_transcript_exon_variant	Exon 9 of 14
LOC105378891	XR_007066273.1	n.148-3616C>T		intron_variant	Intron 2 of 4
LOC105378891	XR_947687.3	n.123-3616C>T		intron_variant	Intron 2 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AKNAD1	ENST00000370001.8	c.1823G>A	p.Arg608His	missense_variant	Exon 10 of 16	1	NM_152763.5	ENSP00000359018.3

Frequencies

GnomAD3 genomes AF: 0.00591 AC: 899 AN: 152162 Hom.: 12 Cov.: 32

Gnomad AFR AF: 0.0208

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00105

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000191

Gnomad OTH AF: 0.00383

GnomAD2 exomes AF: 0.00160 AC: 401 AN: 251184 AF XY: 0.00121

Gnomad AFR exome AF: 0.0214

Gnomad AMR exome AF: 0.000838

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000141

Gnomad OTH exome AF: 0.000978

GnomAD4 exome AF: 0.000633 AC: 926 AN: 1461730 Hom.: 9 Cov.: 31 AF XY: 0.000556 AC XY: 404 AN XY: 727172

African (AFR) AF: 0.0203 AC: 679 AN: 33478

American (AMR) AF: 0.000872 AC: 39 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39700

South Asian (SAS) AF: 0.0000812 AC: 7 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53274

Middle Eastern (MID) AF: 0.000520 AC: 3 AN: 5768

European-Non Finnish (NFE) AF: 0.0000962 AC: 107 AN: 1112000

Other (OTH) AF: 0.00147 AC: 89 AN: 60394

GnomAD4 genome AF: 0.00592 AC: 902 AN: 152280 Hom.: 12 Cov.: 32 AF XY: 0.00583 AC XY: 434 AN XY: 74472

African (AFR) AF: 0.0208 AC: 865 AN: 41558

American (AMR) AF: 0.00105 AC: 16 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000191 AC: 13 AN: 68016

Other (OTH) AF: 0.00379 AC: 8 AN: 2112

Alfa AF: 0.00156 Hom.: 1

Bravo AF: 0.00631

ESP6500AA AF: 0.0211 AC: 93

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.00198 AC: 241

EpiCase AF: 0.000109

EpiControl AF: 0.000296

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.74	T
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.3
DANN	Benign	0.93
DEOGEN2	Benign	0.0015	T;.;.
Eigen	Benign	-0.99
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.0019	N
LIST_S2	Benign	0.74	T;T;T
MetaRNN	Benign	0.0035	T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.0	N;.;N
PhyloP100		-0.55
PrimateAI	Benign	0.18	T
PROVEAN	Benign	0.77	N;N;N
REVEL	Benign	0.022
Sift	Benign	0.34	T;T;T
Sift4G	Benign	0.18	T;T;T
Polyphen		0.0010	B;.;.
Vest4		0.091
MVP		0.014
MPC		0.029
ClinPred		0.0050	T
GERP RS		-2.1
Varity_R		0.033
gMVP		0.040
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs143433407; hg19: chr1-109373196; COSMIC: COSV62201003;