Variant 9-127868151-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000476.3(AK1):c.517-75T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0938 in 1,549,682 control chromosomes in the GnomAD database, including 10,209 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.16 ( 3294 hom., cov: 32)

Exomes 𝑓: 0.086 ( 6915 hom. )

Consequence

AK1
NM_000476.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.145

Variant links:

Genes affected

AK1 (HGNC:361): (adenylate kinase 1) This gene encodes an adenylate kinase enzyme involved in energy metabolism and homeostasis of cellular adenine nucleotide ratios in different intracellular compartments. This gene is highly expressed in skeletal muscle, brain and erythrocytes. Certain mutations in this gene resulting in a functionally inadequate enzyme are associated with a rare genetic disorder causing nonspherocytic hemolytic anemia. Alternative splicing of this gene results in multiple transcript variants encoding different isoforms. This gene shares readthrough transcripts with the upstream ST6GALNAC6 gene. [provided by RefSeq, Jan 2022]

AK1 links:

ST6GALNAC4-ST6GALNAC6-AK1 (HGNC:):

ST6GALNAC4-ST6GALNAC6-AK1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 9-127868151-A-G is Benign according to our data. Variant chr9-127868151-A-G is described in ClinVar as [Benign]. Clinvar id is 1273254.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.361 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AK1	NM_000476.3 linkuse as main transcript	c.517-75T>C		intron_variant		ENST00000644144.2	NP_000467.1
ST6GALNAC4-ST6GALNAC6-AK1	NR_174625.1 linkuse as main transcript	n.3836-75T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AK1	ENST00000644144.2 linkuse as main transcript	c.517-75T>C		intron_variant			NM_000476.3	ENSP00000494600	P1

Frequencies

GnomAD3 genomes

AF:

0.164

AC:

24905

AN:

151932

Hom.:

3286

Cov.:

show subpopulations

Gnomad AFR

AF:

0.366

Gnomad AMI

AF:

0.0647

Gnomad AMR

AF:

0.110

Gnomad ASJ

AF:

0.0988

Gnomad EAS

AF:

0.0784

Gnomad SAS

AF:

0.0468

Gnomad FIN

AF:

0.0588

Gnomad MID

AF:

0.166

Gnomad NFE

AF:

0.0891

Gnomad OTH

AF:

0.153

GnomAD4 exome

AF:

0.0862

AC:

120494

AN:

1397632

Hom.:

6915

Cov.:

AF XY:

0.0849

AC XY:

59335

AN XY:

698656

show subpopulations

Gnomad4 AFR exome

AF:

0.379

Gnomad4 AMR exome

AF:

0.0684

Gnomad4 ASJ exome

AF:

0.0954

Gnomad4 EAS exome

AF:

0.0780

Gnomad4 SAS exome

AF:

0.0515

Gnomad4 FIN exome

AF:

0.0655

Gnomad4 NFE exome

AF:

0.0809

Gnomad4 OTH exome

AF:

0.0980

GnomAD4 genome

AF:

0.164

AC:

24937

AN:

152050

Hom.:

3294

Cov.:

AF XY:

0.161

AC XY:

11987

AN XY:

74322

show subpopulations

Gnomad4 AFR

AF:

0.366

Gnomad4 AMR

AF:

0.110

Gnomad4 ASJ

AF:

0.0988

Gnomad4 EAS

AF:

0.0781

Gnomad4 SAS

AF:

0.0471

Gnomad4 FIN

AF:

0.0588

Gnomad4 NFE

AF:

0.0891

Gnomad4 OTH

AF:

0.150

Alfa

AF:

0.124

Hom.:

322

Bravo

AF:

0.176

Asia WGS

AF:

0.0730

AC:

255

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 18, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

1.9

DANN

Benign

0.83

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over