14-96449891-C-T

Variant names:

• chr14-96449891-C-T
• rs10444759
• NM_152327.5:c.948+12C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_152327.5(AK7):​c.948+12C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.36 in 1,464,326 control chromosomes in the GnomAD database, including 96,230 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.44 (8554 hom., cov: 30)
  • Exomes 𝑓: 0.35 (87676 hom.)
• Consequence: AK7 NM_152327.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.76
• Publications: 7 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: ClinGen, Ambry Genetics
• spermatogenic failure 27

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

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BP6: Variant 14-96449891-C-T is Benign according to our data. Variant chr14-96449891-C-T is described in ClinVar as Benign. ClinVar VariationId is 402361.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.454 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AK7	NM_152327.5	MANE Select	c.948+12C>T		intron	N/A	NP_689540.2	Q96M32
	AK7	NM_001350888.2		c.948+12C>T		intron	N/A	NP_001337817.1
	AK7	NM_001350890.2		c.948+12C>T		intron	N/A	NP_001337819.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AK7	ENST00000267584.9	TSL:1 MANE Select	c.948+12C>T		intron	N/A	ENSP00000267584.4	Q96M32
	AK7	ENST00000856706.1		c.1032+12C>T		intron	N/A	ENSP00000526765.1
	AK7	ENST00000856705.1		c.948+12C>T		intron	N/A	ENSP00000526764.1

Frequencies

GnomAD3 genomes AF: 0.437 AC: 49689 AN: 113812 Hom.: 8559 Cov.: 30

Gnomad AFR AF: 0.442

Gnomad AMI AF: 0.445

Gnomad AMR AF: 0.465

Gnomad ASJ AF: 0.494

Gnomad EAS AF: 0.341

Gnomad SAS AF: 0.460

Gnomad FIN AF: 0.374

Gnomad MID AF: 0.521

Gnomad NFE AF: 0.436

Gnomad OTH AF: 0.476

GnomAD2 exomes AF: 0.393 AC: 72893 AN: 185608 AF XY: 0.396

Gnomad AFR exome AF: 0.305

Gnomad AMR exome AF: 0.423

Gnomad ASJ exome AF: 0.464

Gnomad EAS exome AF: 0.235

Gnomad FIN exome AF: 0.336

Gnomad NFE exome AF: 0.412

Gnomad OTH exome AF: 0.425

GnomAD4 exome AF: 0.354 AC: 478176 AN: 1350472 Hom.: 87676 Cov.: 25 AF XY: 0.357 AC XY: 240842 AN XY: 674194

African (AFR) AF: 0.242 AC: 7168 AN: 29588

American (AMR) AF: 0.381 AC: 13732 AN: 36006

Ashkenazi Jewish (ASJ) AF: 0.427 AC: 10327 AN: 24196

East Asian (EAS) AF: 0.152 AC: 5873 AN: 38708

South Asian (SAS) AF: 0.407 AC: 31796 AN: 78140

European-Finnish (FIN) AF: 0.322 AC: 16505 AN: 51248

Middle Eastern (MID) AF: 0.444 AC: 2047 AN: 4610

European-Non Finnish (NFE) AF: 0.359 AC: 370406 AN: 1032034

Other (OTH) AF: 0.363 AC: 20322 AN: 55942

GnomAD4 genome AF: 0.436 AC: 49681 AN: 113854 Hom.: 8554 Cov.: 30 AF XY: 0.435 AC XY: 24165 AN XY: 55516

African (AFR) AF: 0.442 AC: 10470 AN: 23692

American (AMR) AF: 0.464 AC: 5656 AN: 12180

Ashkenazi Jewish (ASJ) AF: 0.494 AC: 1435 AN: 2902

East Asian (EAS) AF: 0.342 AC: 957 AN: 2800

South Asian (SAS) AF: 0.459 AC: 1910 AN: 4164

European-Finnish (FIN) AF: 0.374 AC: 3093 AN: 8266

Middle Eastern (MID) AF: 0.518 AC: 115 AN: 222

European-Non Finnish (NFE) AF: 0.436 AC: 24986 AN: 57342

Other (OTH) AF: 0.472 AC: 738 AN: 1564

Alfa AF: 0.356 Hom.: 24190

Bravo AF: 0.328

Asia WGS AF: 0.274 AC: 944 AN: 3450

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.028
DANN	Benign	0.51
PhyloP100		-1.8
Mutation Taster		=100/0	polymorphism (auto)

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: rs10444759; hg19: chr14-96916228;