6-109506526-A-G

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_001145128.3(AK9):c.4650T>C(p.Asn1550=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00272 in 1,593,962 control chromosomes in the GnomAD database, including 110 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.015 (58 hom., cov: 32)
  • Exomes 𝑓: 0.0015 (52 hom.)
• Consequence: AK9 NM_001145128.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0340

Genes affected

AK9 (HGNC:33814): (adenylate kinase 9) The protein encoded by this gene catalyzes the interconversion of nucleosides, possessing both nucleoside monophosphate and diphosphate kinase activities. The encoded protein uses these interconversions to maintain nucleoside homeostasis. [provided by RefSeq, Jul 2016]

ZBTB24-DT (HGNC:55872): (ZBTB24 divergent transcript)

ACMG classification

Verdict is Benign. Variant got -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BP6: Variant 6-109506526-A-G is Benign according to our data. Variant chr6-109506526-A-G is described in ClinVar as [Benign]. Clinvar id is 778890.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.034 with no splicing effect.
• BA1: GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0505 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AK9	NM_001145128.3	c.4650T>C	p.Asn1550=	synonymous_variant	35/41	ENST00000424296.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AK9	ENST00000424296.7	c.4650T>C	p.Asn1550=	synonymous_variant	35/41	5	NM_001145128.3	P1
ZBTB24-DT	ENST00000658720.1	n.1429-151A>G		intron_variant, non_coding_transcript_variant
AK9	ENST00000470564.5	c.1164T>C	p.Asn388=	synonymous_variant	8/14	5
ZBTB24-DT	ENST00000423747.2	n.259-151A>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0147 AC: 2237 AN: 152180 Hom.: 58 Cov.: 32

Gnomad AFR AF: 0.0515

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00445

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000206

Gnomad OTH AF: 0.00812

GnomAD3 exomes AF: 0.00370 AC: 800 AN: 215972 Hom.: 18 AF XY: 0.00292 AC XY: 340 AN XY: 116582

Gnomad AFR exome AF: 0.0535

Gnomad AMR exome AF: 0.00185

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000151

Gnomad OTH exome AF: 0.00145

GnomAD4 exome AF: 0.00145 AC: 2095 AN: 1441664 Hom.: 52 Cov.: 32 AF XY: 0.00121 AC XY: 869 AN XY: 715410

Gnomad4 AFR exome AF: 0.0526

Gnomad4 AMR exome AF: 0.00221

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000236

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000591

Gnomad4 OTH exome AF: 0.00322

GnomAD4 genome AF: 0.0147 AC: 2240 AN: 152298 Hom.: 58 Cov.: 32 AF XY: 0.0142 AC XY: 1059 AN XY: 74476

Gnomad4 AFR AF: 0.0515

Gnomad4 AMR AF: 0.00444

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000206

Gnomad4 OTH AF: 0.00803

Alfa AF: 0.00796 Hom.: 10

Bravo AF: 0.0164

Asia WGS AF: 0.00260 AC: 9 AN: 3476

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

Invitae

Apr 30, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
Cadd	Benign	0.24
Dann	Benign	0.57

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: rs78704011; hg19: chr6-109827729;