1-108823418-C-T

Variant names:

• chr1-108823418-C-T
• rs1663885173
• NM_152763.5:c.2119G>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_152763.5(AKNAD1):​c.2119G>A​(p.Ala707Thr) 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. 15/26 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: AKNAD1 NM_152763.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.138
• Publications: 0 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]

ENSG00000301958 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AKNAD1	NM_152763.5	c.2119G>A	p.Ala707Thr	missense_variant	Exon 13 of 16	ENST00000370001.8	NP_689976.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AKNAD1	ENST00000370001.8	c.2119G>A	p.Ala707Thr	missense_variant	Exon 13 of 16	1	NM_152763.5	ENSP00000359018.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 21, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2119G>A (p.A707T) alteration is located in exon 13 (coding exon 12) of the AKNAD1 gene. This alteration results from a G to A substitution at nucleotide position 2119, causing the alanine (A) at amino acid position 707 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	0.080
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	7.0
DANN	Benign	0.86
DEOGEN2	Benign	0.0010	T;.;.
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.017	N
LIST_S2	Benign	0.56	T;T;T
M_CAP	Benign	0.0023	T
MetaRNN	Benign	0.057	T;T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.63	N;.;N
PhyloP100		-0.14
PrimateAI	Benign	0.26	T
PROVEAN	Benign	0.030	N;N;N
REVEL	Benign	0.020
Sift	Benign	0.21	T;T;T
Sift4G	Benign	0.79	T;T;T
Polyphen		0.0030	B;.;.
Vest4		0.087
MutPred		0.18		Loss of sheet (P = 0.0181);.;Loss of sheet (P = 0.0181);
MVP		0.014
MPC		0.027
ClinPred		0.33	T
GERP RS		-1.0
Varity_R		0.040
gMVP		0.021
Mutation Taster		=96/4	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.35		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.27		Position offset: 3
DS_DL_spliceai		0.35		Position offset: -48

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

Other links and lift over

dbSNP: rs1663885173; hg19: chr1-109366040;