14-96392254-G-C

Variant names:

• chr14-96392254-G-C
• rs761681729
• NM_152327.5:c.100G>C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_152327.5(AK7):​c.100G>C​(p.Gly34Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000548 in 1,459,550 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000055 (0 hom.)
• Consequence: AK7 NM_152327.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.40

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.829

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AK7	NM_152327.5	c.100G>C	p.Gly34Arg	missense_variant	Exon 1 of 18	ENST00000267584.9	NP_689540.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AK7	ENST00000267584.9	c.100G>C	p.Gly34Arg	missense_variant	Exon 1 of 18	1	NM_152327.5	ENSP00000267584.4
AK7	ENST00000555570.1	c.100G>C	p.Gly34Arg	missense_variant	Exon 1 of 2	2		ENSP00000451068.1
AK7	ENST00000556643.1	n.111G>C		non_coding_transcript_exon_variant	Exon 1 of 3	2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD3 exomes AF: 0.00000399 AC: 1 AN: 250628 Hom.: 0 AF XY: 0.00000737 AC XY: 1 AN XY: 135610

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000883

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000548 AC: 8 AN: 1459550 Hom.: 0 Cov.: 30 AF XY: 0.00000689 AC XY: 5 AN XY: 726126

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000721

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.98
BayesDel_addAF	Pathogenic	0.29	D
BayesDel_noAF	Pathogenic	0.18
CADD	Pathogenic	29
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.31	T;.
Eigen	Uncertain	0.65
Eigen_PC	Uncertain	0.61
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Uncertain	0.89	D;D
M_CAP	Benign	0.052	D
MetaRNN	Pathogenic	0.83	D;D
MetaSVM	Benign	-0.35	T
MutationAssessor	Uncertain	2.6	M;.
PrimateAI	Uncertain	0.74	T
PROVEAN	Uncertain	-2.9	D;D
REVEL	Uncertain	0.36
Sift	Uncertain	0.014	D;D
Sift4G	Uncertain	0.019	D;D
Polyphen		0.99	D;D
Vest4		0.86
MutPred		0.42		Gain of MoRF binding (P = 0.0141);Gain of MoRF binding (P = 0.0141);
MVP		0.81
MPC		0.32
ClinPred		0.97	D
GERP RS		4.7
Varity_R		0.55
gMVP		0.87

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

Publications

LitVar

Other links and lift over

dbSNP: rs761681729; hg19: chr14-96858591;