14-96398068-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_152327.5(AK7):c.106-7C>A variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: AK7 NM_152327.5 splice_region, splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.09708
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.614

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AK7	NM_152327.5	c.106-7C>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000267584.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AK7	ENST00000267584.9	c.106-7C>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_152327.5	P1
AK7	ENST00000555570.1	c.106-7C>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		2
AK7	ENST00000556643.1	n.117-7C>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Invitae

Mar 18, 2023

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. This variant has not been reported in the literature in individuals affected with AK7-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change falls in intron 1 of the AK7 gene. It does not directly change the encoded amino acid sequence of the AK7 protein. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
Cadd	Benign	17
Dann	Benign	0.60

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.097
dbscSNV1_RF	Benign	0.32
SpliceAI score (max)		0.44		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.44		Position offset: 26

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr14-96864405;