rs377315557

Variant names:

• chr9-132878252-C-T
• rs377315557
• NM_152572.3:c.4G>A

Your query was ambiguous. Multiple possible variants found:

• chr9-132878252-C-T
• chr9-132878252-C-A
• chr9-132878252-C-G

Variant summary

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

The NM_152572.3(AK8):​c.4G>A​(p.Asp2Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000433 in 1,385,652 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000024 (0 hom.)
• Consequence: AK8 NM_152572.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.26
• Publications: 1 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]

SPACA9 (HGNC:1367): (sperm acrosome associated 9) Predicted to enable calcium-dependent protein binding activity. Located in cytoplasmic microtubule. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152572.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AK8	NM_152572.3	MANE Select	c.4G>A	p.Asp2Asn	missense	Exon 1 of 13	NP_689785.1	Q96MA6-1
	AK8	NM_001371772.1		c.4G>A	p.Asp2Asn	missense	Exon 1 of 11	NP_001358701.1
	AK8	NM_001317959.2		c.-906G>A		5_prime_UTR	Exon 1 of 15	NP_001304888.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AK8	ENST00000298545.4	TSL:1 MANE Select	c.4G>A	p.Asp2Asn	missense	Exon 1 of 13	ENSP00000298545.3	Q96MA6-1
	SPACA9	ENST00000372136.7	TSL:1	c.-222C>T		5_prime_UTR	Exon 1 of 4	ENSP00000361209.3	Q96E40-1
	AK8	ENST00000885294.1		c.4G>A	p.Asp2Asn	missense	Exon 1 of 13	ENSP00000555353.1

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152152 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00 AC: 0 AN: 119154 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000243 AC: 3 AN: 1233500 Hom.: 0 Cov.: 29 AF XY: 0.00000167 AC XY: 1 AN XY: 598194

African (AFR) AF: 0.000119 AC: 3 AN: 25228

American (AMR) AF: 0.00 AC: 0 AN: 20544

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16546

East Asian (EAS) AF: 0.00 AC: 0 AN: 31718

South Asian (SAS) AF: 0.00 AC: 0 AN: 47160

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 44654

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4574

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 993578

Other (OTH) AF: 0.00 AC: 0 AN: 49498

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152152 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74342

African (AFR) AF: 0.0000724 AC: 3 AN: 41450

American (AMR) AF: 0.00 AC: 0 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68000

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000378

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00000887 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.64
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.36
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.17	T
Eigen	Uncertain	0.47
Eigen_PC	Uncertain	0.36
FATHMM_MKL	Benign	0.73	D
LIST_S2	Benign	0.28	T
M_CAP	Pathogenic	0.65	D
MetaRNN	Uncertain	0.73	D
MetaSVM	Uncertain	0.27	D
MutationAssessor	Uncertain	2.7	M
PhyloP100		3.3
PrimateAI	Pathogenic	0.80	T
PROVEAN	Uncertain	-2.9	D
REVEL	Uncertain	0.33
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.36
MVP		0.75
MPC		0.51
ClinPred		0.99	D
GERP RS		4.6
PromoterAI		-0.21	Neutral
Varity_R		0.70
gMVP		0.48
Mutation Taster		=277/23	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: rs377315557; hg19: chr9-135753639;