chr1-77333260-C-T

Variant names:

• chr1-77333260-C-T
• rs2815326
• NM_174858.3:c.700-7117C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_174858.3(AK5):​c.700-7117C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.153 in 152,078 control chromosomes in the GnomAD database, including 2,262 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.15 (2262 hom., cov: 32)
• Consequence: AK5 NM_174858.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.157
• Publications: 5 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.204 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_174858.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AK5	NM_174858.3	MANE Select	c.700-7117C>T		intron	N/A	NP_777283.1
	AK5	NM_012093.4		c.622-7117C>T		intron	N/A	NP_036225.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AK5	ENST00000354567.7	TSL:1 MANE Select	c.700-7117C>T		intron	N/A	ENSP00000346577.2
	AK5	ENST00000344720.9	TSL:1	c.622-7117C>T		intron	N/A	ENSP00000341430.5
	AK5	ENST00000524494.1	TSL:4	n.94-7117C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.153 AC: 23285 AN: 151960 Hom.: 2265 Cov.: 32

Gnomad AFR AF: 0.0508

Gnomad AMI AF: 0.199

Gnomad AMR AF: 0.115

Gnomad ASJ AF: 0.0949

Gnomad EAS AF: 0.148

Gnomad SAS AF: 0.109

Gnomad FIN AF: 0.301

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.207

Gnomad OTH AF: 0.150

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.153 AC: 23271 AN: 152078 Hom.: 2262 Cov.: 32 AF XY: 0.155 AC XY: 11531 AN XY: 74326

African (AFR) AF: 0.0507 AC: 2103 AN: 41510

American (AMR) AF: 0.114 AC: 1748 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0949 AC: 329 AN: 3468

East Asian (EAS) AF: 0.147 AC: 763 AN: 5174

South Asian (SAS) AF: 0.108 AC: 520 AN: 4822

European-Finnish (FIN) AF: 0.301 AC: 3176 AN: 10536

Middle Eastern (MID) AF: 0.143 AC: 42 AN: 294

European-Non Finnish (NFE) AF: 0.207 AC: 14092 AN: 67974

Other (OTH) AF: 0.150 AC: 317 AN: 2110

Alfa AF: 0.165 Hom.: 378

Bravo AF: 0.137

Asia WGS AF: 0.134 AC: 466 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	4.2
DANN	Benign	0.61
PhyloP100		-0.16
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: rs2815326; hg19: chr1-77798945;