9-127867954-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.00400

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]

ST6GALNAC4-ST6GALNAC6-AK1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 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_single_submitter, 1 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	UniProt
AK1	NM_000476.3	c.*54C>A		3_prime_UTR_variant	7/7	ENST00000644144.2
ST6GALNAC4-ST6GALNAC6-AK1	NR_174625.1	n.3958C>A		non_coding_transcript_exon_variant	15/15

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.685 AC: 104143 AN: 152030 Hom.: 37960 Cov.: 34

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.: 26 AF XY: 0.788 AC XY: 560774 AN XY: 711878

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.: 34 AF XY: 0.686 AC XY: 50998 AN XY: 74394

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:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

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

Other links and lift over

dbSNP: rs4226; hg19: chr9-130630233; COSMIC: COSV56345209; COSMIC: COSV56345209;