1-77293816-C-T

Position:

• chr1-77293816-C-T

Variant summary

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

The NM_174858.3(AK5):​c.271C>T​(p.Pro91Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: AK5 NM_174858.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.83

Genes affected

AK5 (HGNC:365): (adenylate kinase 5) This gene encodes a member of the adenylate kinase family, which is involved in regulating the adenine nucleotide composition within a cell by catalyzing the reversible transfer of phosphate groups among adenine nucleotides. This member is related to the UMP/CMP kinase of several species. It is located in the cytosol and expressed exclusively in brain. Alternatively spliced transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Jul 2008]

AK5 (HGNC:):

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 (MetaRNN=0.25932705).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AK5	NM_174858.3	c.271C>T	p.Pro91Ser	missense_variant	3/14	ENST00000354567.7	NP_777283.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AK5	ENST00000354567.7	c.271C>T	p.Pro91Ser	missense_variant	3/14	1	NM_174858.3	ENSP00000346577.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 27, 2024

The c.271C>T (p.P91S) alteration is located in exon 3 (coding exon 3) of the AK5 gene. This alteration results from a C to T substitution at nucleotide position 271, causing the proline (P) at amino acid position 91 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Benign	-0.014	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.077	T;.;T
Eigen	Benign	-0.33
Eigen_PC	Benign	-0.13
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.81	T;T;T
M_CAP	Benign	0.038	D
MetaRNN	Benign	0.26	T;T;T
MetaSVM	Benign	-0.67	T
MutationAssessor	Benign	1.9	L;.;.
PrimateAI	Uncertain	0.66	T
PROVEAN	Uncertain	-3.1	D;D;D
REVEL	Benign	0.21
Sift	Uncertain	0.0030	D;D;T
Sift4G	Benign	0.10	T;T;T
Polyphen		0.0010	B;.;.
Vest4		0.35
MutPred		0.28		Gain of phosphorylation at P91 (P = 0.0473);.;.;
MVP		0.69
MPC		0.89
ClinPred		0.97	D
GERP RS		4.4
Varity_R		0.31
gMVP		0.61

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-77759501;