1-77417727-C-T

Variant names:

• chr1-77417727-C-T
• rs1532507
• NM_174858.3:c.1059+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_174858.3(AK5):​c.1059+12C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.127 in 1,508,818 control chromosomes in the GnomAD database, including 12,933 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.13 (1457 hom., cov: 32)
  • Exomes 𝑓: 0.13 (11476 hom.)
• Consequence: AK5 NM_174858.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.335
• Publications: 9 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant 1-77417727-C-T is Benign according to our data. Variant chr1-77417727-C-T is described in ClinVar as Benign. ClinVar VariationId is 402357.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.163 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AK5	NM_174858.3	c.1059+12C>T		intron_variant	Intron 8 of 13	ENST00000354567.7	NP_777283.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AK5	ENST00000354567.7	c.1059+12C>T		intron_variant	Intron 8 of 13	1	NM_174858.3	ENSP00000346577.2

Frequencies

GnomAD3 genomes AF: 0.135 AC: 20510 AN: 152022 Hom.: 1454 Cov.: 32

Gnomad AFR AF: 0.122

Gnomad AMI AF: 0.147

Gnomad AMR AF: 0.169

Gnomad ASJ AF: 0.236

Gnomad EAS AF: 0.120

Gnomad SAS AF: 0.123

Gnomad FIN AF: 0.129

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.131

Gnomad OTH AF: 0.173

GnomAD2 exomes AF: 0.135 AC: 32179 AN: 238712 AF XY: 0.136

Gnomad AFR exome AF: 0.117

Gnomad AMR exome AF: 0.140

Gnomad ASJ exome AF: 0.243

Gnomad EAS exome AF: 0.121

Gnomad FIN exome AF: 0.123

Gnomad NFE exome AF: 0.134

Gnomad OTH exome AF: 0.151

GnomAD4 exome AF: 0.126 AC: 171182 AN: 1356678 Hom.: 11476 Cov.: 21 AF XY: 0.127 AC XY: 86428 AN XY: 679360

African (AFR) AF: 0.120 AC: 3711 AN: 30996

American (AMR) AF: 0.142 AC: 5935 AN: 41896

Ashkenazi Jewish (ASJ) AF: 0.238 AC: 5981 AN: 25112

East Asian (EAS) AF: 0.135 AC: 5252 AN: 38952

South Asian (SAS) AF: 0.124 AC: 10047 AN: 81062

European-Finnish (FIN) AF: 0.122 AC: 6395 AN: 52340

Middle Eastern (MID) AF: 0.191 AC: 1047 AN: 5468

European-Non Finnish (NFE) AF: 0.122 AC: 124611 AN: 1024110

Other (OTH) AF: 0.145 AC: 8203 AN: 56742

GnomAD4 genome AF: 0.135 AC: 20530 AN: 152140 Hom.: 1457 Cov.: 32 AF XY: 0.136 AC XY: 10112 AN XY: 74376

African (AFR) AF: 0.123 AC: 5096 AN: 41520

American (AMR) AF: 0.169 AC: 2575 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.236 AC: 818 AN: 3468

East Asian (EAS) AF: 0.120 AC: 618 AN: 5170

South Asian (SAS) AF: 0.123 AC: 594 AN: 4818

European-Finnish (FIN) AF: 0.129 AC: 1368 AN: 10588

Middle Eastern (MID) AF: 0.184 AC: 54 AN: 294

European-Non Finnish (NFE) AF: 0.131 AC: 8904 AN: 67988

Other (OTH) AF: 0.175 AC: 369 AN: 2112

Alfa AF: 0.140 Hom.: 626

Bravo AF: 0.137

Asia WGS AF: 0.145 AC: 505 AN: 3474

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	12
DANN	Benign	0.75
PhyloP100		-0.34
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: rs1532507; hg19: chr1-77883412; COSMIC: COSV107412766; COSMIC: COSV107412766;