rs8019939

Variant names:

• chr14-96397972-A-G
• rs8019939
• NM_152327.5:c.106-103A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_152327.5(AK7):​c.106-103A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.645 in 1,207,586 control chromosomes in the GnomAD database, including 252,469 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.64 (31735 hom., cov: 32)
  • Exomes 𝑓: 0.64 (220734 hom.)
• Consequence: AK7 NM_152327.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.29
• Publications: 5 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: Ambry Genetics, ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.809 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AK7	NM_152327.5	MANE Select	c.106-103A>G		intron	N/A	NP_689540.2
	AK7	NM_001350888.2		c.106-103A>G		intron	N/A	NP_001337817.1
	AK7	NM_001350890.2		c.106-103A>G		intron	N/A	NP_001337819.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AK7	ENST00000267584.9	TSL:1 MANE Select	c.106-103A>G		intron	N/A	ENSP00000267584.4
	AK7	ENST00000555570.1	TSL:2	c.106-103A>G		intron	N/A	ENSP00000451068.1
	AK7	ENST00000556643.1	TSL:2	n.117-103A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.644 AC: 97910 AN: 151936 Hom.: 31709 Cov.: 32

Gnomad AFR AF: 0.658

Gnomad AMI AF: 0.615

Gnomad AMR AF: 0.593

Gnomad ASJ AF: 0.664

Gnomad EAS AF: 0.830

Gnomad SAS AF: 0.657

Gnomad FIN AF: 0.610

Gnomad MID AF: 0.649

Gnomad NFE AF: 0.638

Gnomad OTH AF: 0.638

GnomAD4 exome AF: 0.645 AC: 680305 AN: 1055532 Hom.: 220734 AF XY: 0.645 AC XY: 343599 AN XY: 533106

African (AFR) AF: 0.655 AC: 16004 AN: 24446

American (AMR) AF: 0.549 AC: 18229 AN: 33204

Ashkenazi Jewish (ASJ) AF: 0.659 AC: 12602 AN: 19114

East Asian (EAS) AF: 0.843 AC: 31765 AN: 37702

South Asian (SAS) AF: 0.653 AC: 42629 AN: 65318

European-Finnish (FIN) AF: 0.624 AC: 23535 AN: 37732

Middle Eastern (MID) AF: 0.603 AC: 1989 AN: 3300

European-Non Finnish (NFE) AF: 0.639 AC: 503721 AN: 788320

Other (OTH) AF: 0.643 AC: 29831 AN: 46396

GnomAD4 genome AF: 0.644 AC: 97996 AN: 152054 Hom.: 31735 Cov.: 32 AF XY: 0.645 AC XY: 47946 AN XY: 74322

African (AFR) AF: 0.658 AC: 27280 AN: 41470

American (AMR) AF: 0.593 AC: 9066 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.664 AC: 2302 AN: 3468

East Asian (EAS) AF: 0.830 AC: 4290 AN: 5170

South Asian (SAS) AF: 0.659 AC: 3173 AN: 4814

European-Finnish (FIN) AF: 0.610 AC: 6446 AN: 10568

Middle Eastern (MID) AF: 0.650 AC: 191 AN: 294

European-Non Finnish (NFE) AF: 0.638 AC: 43339 AN: 67972

Other (OTH) AF: 0.640 AC: 1348 AN: 2106

Alfa AF: 0.637 Hom.: 57875

Bravo AF: 0.642

Asia WGS AF: 0.729 AC: 2538 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.20
DANN	Benign	0.29
PhyloP100		-1.3
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs8019939; hg19: chr14-96864309;