chr9-114342050-C-T

Position:

• chr9-114342050-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001317950.2(AKNA):​c.3833G>A​(p.Gly1278Glu) 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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: AKNA NM_001317950.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.473

Genes affected

AKNA (HGNC:24108): (AT-hook transcription factor) Predicted to enable DNA binding activity. Involved in positive regulation of transcription by RNA polymerase II. Located in centrosome; cytosol; and nuclear lumen. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15474644).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AKNA	NM_001317950.2	c.3833G>A	p.Gly1278Glu	missense_variant	20/22	ENST00000374088.8	NP_001304879.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AKNA	ENST00000374088.8	c.3833G>A	p.Gly1278Glu	missense_variant	20/22	2	NM_001317950.2	ENSP00000363201	P3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 07, 2023

The c.3833G>A (p.G1278E) alteration is located in exon 20 (coding exon 19) of the AKNA gene. This alteration results from a G to A substitution at nucleotide position 3833, causing the glycine (G) at amino acid position 1278 to be replaced by a glutamic acid (E). 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	0.12
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	8.0
DANN	Benign	0.73
DEOGEN2	Benign	0.012	T;T;.;.;.
Eigen	Benign	-0.54
Eigen_PC	Benign	-0.66
FATHMM_MKL	Benign	0.089	N
LIST_S2	Benign	0.62	T;.;T;T;T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.15	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.2	L;L;.;.;.
MutationTaster	Benign	1.0	N;N;N;N;N
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-2.1	N;N;D;N;N
REVEL	Benign	0.0070
Sift	Benign	0.19	T;T;T;T;T
Sift4G	Benign	0.71	T;T;T;T;T
Polyphen		0.16	B;B;.;.;B
Vest4		0.27
MutPred		0.19		Loss of glycosylation at S1279 (P = 0.0706);Loss of glycosylation at S1279 (P = 0.0706);.;.;.;
MVP		0.80
MPC		0.11
ClinPred		0.066	T
GERP RS		1.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.033
gMVP		0.18

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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.

Other links and lift over

hg19: chr9-117104330;