chr6-109499214-A-ATAAC

Variant names:

• chr6-109499214-A-ATAAC
• rs1313545397
• NM_001145128.3:c.4872_4875dupGTTA

Variant summary

Our verdict is Pathogenic. The variant received 11 ACMG points: 11P and 0B. PVS1 PM2 PP5

The NM_001145128.3(AK9):​c.4872_4875dupGTTA​(p.Cys1626ValfsTer16) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000715 in 1,399,392 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: AK9 NM_001145128.3 frameshift
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: -0.0860
• Publications: 1 publications found

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

Our verdict: Pathogenic. The variant received 11 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 6-109499214-A-ATAAC is Pathogenic according to our data. Variant chr6-109499214-A-ATAAC is described in ClinVar as Pathogenic. ClinVar VariationId is 2692351.Status of the report is no_assertion_criteria_provided, 0 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001145128.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AK9	NM_001145128.3	MANE Select	c.4872_4875dupGTTA	p.Cys1626ValfsTer16	frameshift	Exon 36 of 41	NP_001138600.2	Q5TCS8-4
	ZBTB24-DT	NR_187591.1		n.1422+4648_1422+4651dupAACT		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AK9	ENST00000424296.7	TSL:5 MANE Select	c.4872_4875dupGTTA	p.Cys1626ValfsTer16	frameshift	Exon 36 of 41	ENSP00000410186.2	Q5TCS8-4
	AK9	ENST00000490722.1	TSL:1	c.92-20_92-17dupGTTA		intron	N/A	ENSP00000419758.1	H0Y8C5
	AK9	ENST00000470564.5	TSL:5	c.1383_1386dupGTTA	p.Cys463fs	frameshift	Exon 9 of 14	ENSP00000418771.1	H7C517

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000460 AC: 1 AN: 217522 AF XY: 0.00000847

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000623

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 7.15e-7 AC: 1 AN: 1399392 Hom.: 0 Cov.: 30 AF XY: 0.00000145 AC XY: 1 AN XY: 690240

African (AFR) AF: 0.00 AC: 0 AN: 31106

American (AMR) AF: 0.00 AC: 0 AN: 35038

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24138

East Asian (EAS) AF: 0.0000263 AC: 1 AN: 38010

South Asian (SAS) AF: 0.00 AC: 0 AN: 77092

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52462

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5522

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1078472

Other (OTH) AF: 0.00 AC: 0 AN: 57552

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Pathogenic

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
1	-	-	Spermatogenic failure 89 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.086
Mutation Taster		=15/185	disease causing (fs/PTC)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1313545397; hg19: chr6-109820417;