1-108827292-C-T

Variant names:

• chr1-108827292-C-T
• rs779270486
• NM_152763.5:c.1849G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_152763.5(AKNAD1):​c.1849G>A​(p.Val617Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,458,012 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. V617L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: AKNAD1 NM_152763.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0490
• Publications: 3 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: 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=0.05580437).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AKNAD1	NM_152763.5	c.1849G>A	p.Val617Met	missense_variant	Exon 11 of 16	ENST00000370001.8	NP_689976.2
AKNAD1	NR_049760.2	n.2061G>A		non_coding_transcript_exon_variant	Exon 10 of 14
LOC105378891	XR_007066273.1	n.147+3574C>T		intron_variant	Intron 2 of 4
LOC105378891	XR_947687.3	n.122+3574C>T		intron_variant	Intron 2 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AKNAD1	ENST00000370001.8	c.1849G>A	p.Val617Met	missense_variant	Exon 11 of 16	1	NM_152763.5	ENSP00000359018.3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1458012 Hom.: 0 Cov.: 32 AF XY: 0.00000276 AC XY: 2 AN XY: 725446

African (AFR) AF: 0.00 AC: 0 AN: 33448

American (AMR) AF: 0.00 AC: 0 AN: 44430

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26056

East Asian (EAS) AF: 0.00 AC: 0 AN: 39022

South Asian (SAS) AF: 0.00 AC: 0 AN: 85926

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53410

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5704

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1109784

Other (OTH) AF: 0.00 AC: 0 AN: 60232

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.080
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.1
DANN	Benign	0.11
DEOGEN2	Benign	0.0013	T;.;.
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.0011	N
LIST_S2	Benign	0.65	T;T;T
M_CAP	Benign	0.0018	T
MetaRNN	Benign	0.056	T;T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	-0.55	N;.;N
PhyloP100		-0.049
PrimateAI	Benign	0.25	T
PROVEAN	Benign	0.57	N;N;N
REVEL	Benign	0.033
Sift	Benign	1.0	T;T;T
Sift4G	Benign	0.46	T;T;T
Polyphen		0.010	B;.;.
Vest4		0.042
MutPred		0.29		Loss of helix (P = 3e-04);.;Loss of helix (P = 3e-04);
MVP		0.014
MPC		0.026
ClinPred		0.056	T
GERP RS		-1.7
Varity_R		0.022
gMVP		0.031
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs779270486; hg19: chr1-109369914; COSMIC: COSV62198420;