9-127871620-G-C

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.324+203C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.368 in 150,940 control chromosomes in the GnomAD database, including 10,993 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.37 (10993 hom., cov: 32)
• Consequence: AK1 NM_000476.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.207

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=-0.93).
• BP6: Variant 9-127871620-G-C is Benign according to our data. Variant chr9-127871620-G-C is described in ClinVar as [Benign]. Clinvar id is 1236558.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.449 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AK1	NM_000476.3	c.324+203C>G		intron_variant		ENST00000644144.2
ST6GALNAC4-ST6GALNAC6-AK1	NR_174625.1	n.3643+203C>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AK1	ENST00000644144.2	c.324+203C>G		intron_variant			NM_000476.3	P1

Frequencies

GnomAD3 genomes AF: 0.368 AC: 55545 AN: 150820 Hom.: 10974 Cov.: 32

Gnomad AFR AF: 0.446

Gnomad AMI AF: 0.420

Gnomad AMR AF: 0.306

Gnomad ASJ AF: 0.422

Gnomad EAS AF: 0.160

Gnomad SAS AF: 0.463

Gnomad FIN AF: 0.298

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.352

Gnomad OTH AF: 0.370

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.368 AC: 55614 AN: 150940 Hom.: 10993 Cov.: 32 AF XY: 0.364 AC XY: 26829 AN XY: 73760

Gnomad4 AFR AF: 0.446

Gnomad4 AMR AF: 0.306

Gnomad4 ASJ AF: 0.422

Gnomad4 EAS AF: 0.160

Gnomad4 SAS AF: 0.465

Gnomad4 FIN AF: 0.298

Gnomad4 NFE AF: 0.352

Gnomad4 OTH AF: 0.375

Alfa AF: 0.200 Hom.: 390

Bravo AF: 0.368

Asia WGS AF: 0.329 AC: 1143 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	-0.93
Cadd	Benign	5.6
Dann	Benign	0.43

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: rs743540; hg19: chr9-130633899;