rs769228074

Variant names:

• chr9-132792677-C-T
• rs769228074
• NM_152572.3:c.1078G>A

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_152572.3(AK8):​c.1078G>A​(p.Asp360Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00014 in 1,555,386 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00019 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00013 (1 hom.)
• Consequence: AK8 NM_152572.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.66
• Publications: 0 publications found

Genes affected

AK8 (HGNC:26526): (adenylate kinase 8) Enables AMP binding activity and nucleobase-containing compound kinase activity. Involved in nucleoside diphosphate phosphorylation and nucleoside triphosphate biosynthetic process. Located in 9+2 motile cilium. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.2987045).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AK8	NM_152572.3	c.1078G>A	p.Asp360Asn	missense_variant	Exon 11 of 13	ENST00000298545.4	NP_689785.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AK8	ENST00000298545.4	c.1078G>A	p.Asp360Asn	missense_variant	Exon 11 of 13	1	NM_152572.3	ENSP00000298545.3
AK8	ENST00000476719.1	n.1515G>A		non_coding_transcript_exon_variant	Exon 10 of 12	5
AK8	ENST00000477396.5	n.1993G>A		non_coding_transcript_exon_variant	Exon 13 of 15	2

Frequencies

GnomAD3 genomes AF: 0.000184 AC: 28 AN: 152198 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000327

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000309

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000257 AC: 42 AN: 163394 AF XY: 0.000290

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000315

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000128

Gnomad NFE exome AF: 0.000371

Gnomad OTH exome AF: 0.000663

GnomAD4 exome AF: 0.000134 AC: 188 AN: 1403070 Hom.: 1 Cov.: 31 AF XY: 0.000139 AC XY: 96 AN XY: 692560

African (AFR) AF: 0.00 AC: 0 AN: 31926

American (AMR) AF: 0.000219 AC: 8 AN: 36456

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25242

East Asian (EAS) AF: 0.000110 AC: 4 AN: 36292

South Asian (SAS) AF: 0.000151 AC: 12 AN: 79384

European-Finnish (FIN) AF: 0.000121 AC: 6 AN: 49638

Middle Eastern (MID) AF: 0.00120 AC: 5 AN: 4172

European-Non Finnish (NFE) AF: 0.000131 AC: 142 AN: 1081904

Other (OTH) AF: 0.000189 AC: 11 AN: 58056

GnomAD4 genome AF: 0.000190 AC: 29 AN: 152316 Hom.: 0 Cov.: 32 AF XY: 0.000215 AC XY: 16 AN XY: 74486

African (AFR) AF: 0.0000481 AC: 2 AN: 41566

American (AMR) AF: 0.000327 AC: 5 AN: 15304

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.0000941 AC: 1 AN: 10624

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

European-Non Finnish (NFE) AF: 0.000309 AC: 21 AN: 68020

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.000291 Hom.: 0

Bravo AF: 0.000174

ExAC AF: 0.000105 AC: 12

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Oct 08, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1078G>A (p.D360N) alteration is located in exon 11 (coding exon 11) of the AK8 gene. This alteration results from a G to A substitution at nucleotide position 1078, causing the aspartic acid (D) at amino acid position 360 to be replaced by an asparagine (N). 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	0.15
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.35
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.22	T
Eigen	Uncertain	0.33
Eigen_PC	Uncertain	0.34
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.85	T
M_CAP	Uncertain	0.12	D
MetaRNN	Benign	0.30	T
MetaSVM	Uncertain	-0.18	T
MutationAssessor	Benign	1.8	L
PhyloP100		2.7
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.27
Sift	Uncertain	0.011	D
Sift4G	Uncertain	0.041	D
Polyphen		0.91	P
Vest4		0.32
MVP		0.75
MPC		0.51
ClinPred		0.17	T
GERP RS		5.2
Varity_R		0.14
gMVP		0.47
Mutation Taster		=95/5	polymorphism

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

Other links and lift over

dbSNP: rs769228074; hg19: chr9-135668064;