Variant 9-127867954-G-T 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.*54C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.778 in 1,578,842 control chromosomes in the GnomAD database, including 484,622 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.68 ( 37957 hom., cov: 34)

Exomes 𝑓: 0.79 ( 446665 hom. )

Consequence

AK1
NM_000476.3 3_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.00400

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=-0.84).

BP6

Variant 9-127867954-G-T is Benign according to our data. Variant chr9-127867954-G-T is described in ClinVar as [Benign]. Clinvar id is 1232991.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.863 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.*54C>A		3_prime_UTR_variant	7/7	ENST00000644144.2	NP_000467.1
ST6GALNAC4-ST6GALNAC6-AK1	NR_174625.1 linkuse as main transcript	n.3958C>A		non_coding_transcript_exon_variant	15/15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AK1	ENST00000644144.2 linkuse as main transcript	c.*54C>A		3_prime_UTR_variant	7/7		NM_000476.3	ENSP00000494600	P1

Frequencies

GnomAD3 genomes

AF:

0.685

AC:

104143

AN:

152030

Hom.:

37960

Cov.:

show subpopulations

Gnomad AFR

AF:

0.418

Gnomad AMI

AF:

0.864

Gnomad AMR

AF:

0.682

Gnomad ASJ

AF:

0.755

Gnomad EAS

AF:

0.885

Gnomad SAS

AF:

0.741

Gnomad FIN

AF:

0.836

Gnomad MID

AF:

0.696

Gnomad NFE

AF:

0.799

Gnomad OTH

AF:

0.697

GnomAD4 exome

AF:

0.788

AC:

1124404

AN:

1426694

Hom.:

446665

Cov.:

AF XY:

0.788

AC XY:

560774

AN XY:

711878

show subpopulations

Gnomad4 AFR exome

AF:

0.402

Gnomad4 AMR exome

AF:

0.706

Gnomad4 ASJ exome

AF:

0.752

Gnomad4 EAS exome

AF:

0.877

Gnomad4 SAS exome

AF:

0.734

Gnomad4 FIN exome

AF:

0.826

Gnomad4 NFE exome

AF:

0.805

Gnomad4 OTH exome

AF:

0.766

GnomAD4 genome

AF:

0.685

AC:

104159

AN:

152148

Hom.:

37957

Cov.:

AF XY:

0.686

AC XY:

50998

AN XY:

74394

show subpopulations

Gnomad4 AFR

AF:

0.418

Gnomad4 AMR

AF:

0.681

Gnomad4 ASJ

AF:

0.755

Gnomad4 EAS

AF:

0.885

Gnomad4 SAS

AF:

0.741

Gnomad4 FIN

AF:

0.836

Gnomad4 NFE

AF:

0.799

Gnomad4 OTH

AF:

0.698

Alfa

AF:

0.643

Hom.:

3469

Bravo

AF:

0.664

Asia WGS

AF:

0.781

AC:

2717

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	Nov 10, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

1.8

DANN

Benign

0.71

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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