rs746369518

Variant names:

• chr14-96398118-CAGAGGAAGAGGA-C
• rs746369518
• NM_152327.5:c.159_170delGGAAGAGGAAGA

Your query was ambiguous. Multiple possible variants found:

• chr14-96398118-CAGAGGAAGAGGA-C
• chr14-96398118-CAGAGGAAGAGGA-CAGAGGA
• chr14-96398118-CAGAGGAAGAGGA-CAGAGGAAGAGGAAGAGGA

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM4

The NM_152327.5(AK7):​c.159_170delGGAAGAGGAAGA​(p.Glu53_Glu56del) variant causes a disruptive inframe deletion change. The variant allele was found at a frequency of 0.000531 in 1,614,100 control chromosomes in the GnomAD database, including 1 homozygotes. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00032 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00055 (1 hom.)
• Consequence: AK7 NM_152327.5 disruptive_inframe_deletion
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.85
• Publications: 1 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 2 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_152327.5.

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.159_170delGGAAGAGGAAGA	p.Glu53_Glu56del	disruptive_inframe_deletion	Exon 2 of 18	NP_689540.2	Q96M32
	AK7	NM_001350888.2		c.159_170delGGAAGAGGAAGA	p.Glu53_Glu56del	disruptive_inframe_deletion	Exon 2 of 17	NP_001337817.1
	AK7	NM_001350890.2		c.159_170delGGAAGAGGAAGA	p.Glu53_Glu56del	disruptive_inframe_deletion	Exon 2 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.159_170delGGAAGAGGAAGA	p.Glu53_Glu56del	disruptive_inframe_deletion	Exon 2 of 18	ENSP00000267584.4	Q96M32
	AK7	ENST00000856706.1		c.159_170delGGAAGAGGAAGA	p.Glu53_Glu56del	disruptive_inframe_deletion	Exon 2 of 19	ENSP00000526765.1
	AK7	ENST00000856705.1		c.159_170delGGAAGAGGAAGA	p.Glu53_Glu56del	disruptive_inframe_deletion	Exon 2 of 17	ENSP00000526764.1

Frequencies

GnomAD3 genomes AF: 0.000322 AC: 49 AN: 152154 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

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: 0.000588

Gnomad OTH AF: 0.000955

GnomAD2 exomes AF: 0.000374 AC: 94 AN: 251412 AF XY: 0.000390

Gnomad AFR exome AF: 0.000123

Gnomad AMR exome AF: 0.000318

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000677

Gnomad OTH exome AF: 0.000489

GnomAD4 exome AF: 0.000553 AC: 808 AN: 1461828 Hom.: 1 AF XY: 0.000532 AC XY: 387 AN XY: 727224

African (AFR) AF: 0.000209 AC: 7 AN: 33478

American (AMR) AF: 0.000358 AC: 16 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53374

Middle Eastern (MID) AF: 0.000520 AC: 3 AN: 5768

European-Non Finnish (NFE) AF: 0.000671 AC: 746 AN: 1111998

Other (OTH) AF: 0.000563 AC: 34 AN: 60392

GnomAD4 genome AF: 0.000322 AC: 49 AN: 152272 Hom.: 0 Cov.: 32 AF XY: 0.000363 AC XY: 27 AN XY: 74442

African (AFR) AF: 0.0000722 AC: 3 AN: 41558

American (AMR) AF: 0.000262 AC: 4 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10606

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

European-Non Finnish (NFE) AF: 0.000588 AC: 40 AN: 68022

Other (OTH) AF: 0.000945 AC: 2 AN: 2116

Alfa AF: 0.000509 Hom.: 0

Bravo AF: 0.000378

EpiCase AF: 0.000436

EpiControl AF: 0.000652

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
PhyloP100		6.8
Mutation Taster		=126/74	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs746369518; hg19: chr14-96864455; COSMIC: COSV50869232; COSMIC: COSV50869232;