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GeneBe

6-109499194-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_001145128.3(AK9):c.4896G>A(p.Leu1632=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00111 in 1,599,240 control chromosomes in the GnomAD database, including 23 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0061 ( 13 hom., cov: 32)
Exomes 𝑓: 0.00058 ( 10 hom. )

Consequence

AK9
NM_001145128.3 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.404
Variant links:
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)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.6).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 6-109499194-C-T is Benign according to our data. Variant chr6-109499194-C-T is described in ClinVar as [Benign]. Clinvar id is 789748.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=0.404 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00607 (925/152296) while in subpopulation AFR AF= 0.0212 (879/41560). AF 95% confidence interval is 0.02. There are 13 homozygotes in gnomad4. There are 458 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 13 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
AK9NM_001145128.3 linkuse as main transcriptc.4896G>A p.Leu1632= synonymous_variant 36/41 ENST00000424296.7
ZBTB24-DTXR_942855.3 linkuse as main transcriptn.402-2410C>T intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
AK9ENST00000424296.7 linkuse as main transcriptc.4896G>A p.Leu1632= synonymous_variant 36/415 NM_001145128.3 P1Q5TCS8-4
ZBTB24-DTENST00000658720.1 linkuse as main transcriptn.1428+4626C>T intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00607
AC:
924
AN:
152178
Hom.:
13
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0212
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00170
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000414
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.0000882
Gnomad OTH
AF:
0.00526
GnomAD3 exomes
AF:
0.00140
AC:
338
AN:
241348
Hom.:
6
AF XY:
0.000988
AC XY:
129
AN XY:
130558
show subpopulations
Gnomad AFR exome
AF:
0.0190
Gnomad AMR exome
AF:
0.000694
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000142
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000631
Gnomad OTH exome
AF:
0.000515
GnomAD4 exome
AF:
0.000584
AC:
845
AN:
1446944
Hom.:
10
Cov.:
31
AF XY:
0.000504
AC XY:
362
AN XY:
718798
show subpopulations
Gnomad4 AFR exome
AF:
0.0214
Gnomad4 AMR exome
AF:
0.000891
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000598
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000127
Gnomad4 OTH exome
AF:
0.00137
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00607
AC:
925
AN:
152296
Hom.:
13
Cov.:
32
AF XY:
0.00615
AC XY:
458
AN XY:
74478
show subpopulations
Gnomad4 AFR
AF:
0.0212
Gnomad4 AMR
AF:
0.00170
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000414
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000882
Gnomad4 OTH
AF:
0.00520
Alfa
AF:
0.00312
Hom.:
4
Bravo
AF:
0.00675
Asia WGS
AF:
0.00144
AC:
6
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeFeb 26, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.60
Cadd
Benign
5.4
Dann
Benign
0.77

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.

Other links and lift over

dbSNP: rs73520970; hg19: chr6-109820397; API