rs1325974330

Variant names:

• chr14-96392236-T-A
• rs1325974330
• NM_152327.5:c.82T>A

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_152327.5(AK7):​c.82T>A​(p.Tyr28Asn) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: AK7 NM_152327.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.30
• Publications: 0 publications found

Genes affected

AK7 (HGNC:20091): (adenylate kinase 7) This gene encodes a member of the adenylate kinase family of enzymes. The encoded enzyme is a phosphotransferase that catalyzes the reversible phosphorylation of adenine nucleotides. This enzyme plays a role in energy homeostasis of the cell. Alternative splicing results in multiple transcript variants. Mutations in the mouse gene are associated with primary ciliary dyskinesia. [provided by RefSeq, Apr 2017]

AK7 Gene-Disease associations (from GenCC):

• non-syndromic male infertility due to sperm motility disorder

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• primary ciliary dyskinesia

  Inheritance: AR Classification: LIMITED, NO_KNOWN Submitted by: Ambry Genetics, ClinGen
• spermatogenic failure 27

  Inheritance: AR Classification: LIMITED Submitted by: ClinGen, Ambry Genetics

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.852

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152327.5. 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
	AK7	NM_152327.5	MANE Select	c.82T>A	p.Tyr28Asn	missense	Exon 1 of 18	NP_689540.2	Q96M32
	AK7	NM_001350888.2		c.82T>A	p.Tyr28Asn	missense	Exon 1 of 17	NP_001337817.1
	AK7	NM_001350890.2		c.82T>A	p.Tyr28Asn	missense	Exon 1 of 17	NP_001337819.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AK7	ENST00000267584.9	TSL:1 MANE Select	c.82T>A	p.Tyr28Asn	missense	Exon 1 of 18	ENSP00000267584.4	Q96M32
	AK7	ENST00000856706.1		c.82T>A	p.Tyr28Asn	missense	Exon 1 of 19	ENSP00000526765.1
	AK7	ENST00000856705.1		c.82T>A	p.Tyr28Asn	missense	Exon 1 of 17	ENSP00000526764.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251060 AF XY: 0.00000737

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: 0.00000881

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.41
BayesDel_addAF	Pathogenic	0.21	D
BayesDel_noAF	Uncertain	0.060
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Benign	0.39	T
Eigen	Uncertain	0.57
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Uncertain	0.90	D
M_CAP	Uncertain	0.25	D
MetaRNN	Pathogenic	0.85	D
MetaSVM	Uncertain	0.012	D
MutationAssessor	Uncertain	2.8	M
PhyloP100		4.3
PrimateAI	Uncertain	0.64	T
PROVEAN	Pathogenic	-6.8	D
REVEL	Uncertain	0.51
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0010	D
Polyphen		1.0	D
Vest4		0.87
MutPred		0.45		Gain of relative solvent accessibility (P = 0.0166)
MVP		0.88
MPC		0.94
ClinPred		0.99	D
GERP RS		4.7
PromoterAI		0.079	Neutral
Varity_R		0.87
gMVP		0.81
Mutation Taster		=65/35	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: rs1325974330; hg19: chr14-96858573;