9-127868151-A-G

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.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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.145

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=-0.88).
• 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_single_submitter, 1 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	UniProt
AK1	NM_000476.3	c.517-75T>C		intron_variant		ENST00000644144.2
ST6GALNAC4-ST6GALNAC6-AK1	NR_174625.1	n.3836-75T>C		intron_variant, non_coding_transcript_variant

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.164 AC: 24905 AN: 151932 Hom.: 3286 Cov.: 32

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.: 25 AF XY: 0.0849 AC XY: 59335 AN XY: 698656

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.: 32 AF XY: 0.161 AC XY: 11987 AN XY: 74322

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:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 18, 2021

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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

Other links and lift over

dbSNP: rs6478799; hg19: chr9-130630430; COSMIC: COSV56345306; COSMIC: COSV56345306;