rs111419100

Variant names:

• chr14-96392205-C-A
• rs111419100
• NM_152327.5:c.51C>A

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BS1 BS2

The NM_152327.5(AK7):​c.51C>A​(p.Thr17Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00168 in 1,613,752 control chromosomes in the GnomAD database, including 46 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0087 (22 hom., cov: 31)
  • Exomes 𝑓: 0.00094 (24 hom.)
• Consequence: AK7 NM_152327.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.315
• 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: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.3).
• BP6: Variant 14-96392205-C-A is Benign according to our data. Variant chr14-96392205-C-A is described in ClinVar as Benign. ClinVar VariationId is 1653243.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.315 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00871 (1327/152314) while in subpopulation AFR AF = 0.03 (1247/41570). AF 95% confidence interval is 0.0286. There are 22 homozygotes in GnomAd4. There are 606 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 22 AR gene

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.51C>A	p.Thr17Thr	synonymous	Exon 1 of 18	NP_689540.2	Q96M32
	AK7	NM_001350888.2		c.51C>A	p.Thr17Thr	synonymous	Exon 1 of 17	NP_001337817.1
	AK7	NM_001350890.2		c.51C>A	p.Thr17Thr	synonymous	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.51C>A	p.Thr17Thr	synonymous	Exon 1 of 18	ENSP00000267584.4	Q96M32
	AK7	ENST00000856706.1		c.51C>A	p.Thr17Thr	synonymous	Exon 1 of 19	ENSP00000526765.1
	AK7	ENST00000856705.1		c.51C>A	p.Thr17Thr	synonymous	Exon 1 of 17	ENSP00000526764.1

Frequencies

GnomAD3 genomes AF: 0.00869 AC: 1322 AN: 152196 Hom.: 22 Cov.: 31

Gnomad AFR AF: 0.0300

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00301

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000162

Gnomad OTH AF: 0.0100

GnomAD2 exomes AF: 0.00223 AC: 560 AN: 251256 AF XY: 0.00154

Gnomad AFR exome AF: 0.0307

Gnomad AMR exome AF: 0.00116

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000440

Gnomad OTH exome AF: 0.00147

GnomAD4 exome AF: 0.000943 AC: 1378 AN: 1461438 Hom.: 24 Cov.: 30 AF XY: 0.000794 AC XY: 577 AN XY: 727058

African (AFR) AF: 0.0334 AC: 1117 AN: 33458

American (AMR) AF: 0.00136 AC: 61 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26114

East Asian (EAS) AF: 0.00 AC: 0 AN: 39684

South Asian (SAS) AF: 0.000220 AC: 19 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.000693 AC: 4 AN: 5768

European-Non Finnish (NFE) AF: 0.0000261 AC: 29 AN: 1111660

Other (OTH) AF: 0.00245 AC: 148 AN: 60358

GnomAD4 genome AF: 0.00871 AC: 1327 AN: 152314 Hom.: 22 Cov.: 31 AF XY: 0.00814 AC XY: 606 AN XY: 74466

African (AFR) AF: 0.0300 AC: 1247 AN: 41570

American (AMR) AF: 0.00301 AC: 46 AN: 15302

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5164

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

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

European-Non Finnish (NFE) AF: 0.000162 AC: 11 AN: 68036

Other (OTH) AF: 0.00993 AC: 21 AN: 2114

Alfa AF: 0.00342 Hom.: 3

Bravo AF: 0.00992

Asia WGS AF: 0.00260 AC: 9 AN: 3478

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.30
CADD	Benign	6.3
DANN	Benign	0.73
PhyloP100		0.32
PromoterAI		0.00040	Neutral
Mutation Taster		=96/4	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: rs111419100; hg19: chr14-96858542;