chr6-109499129-A-C

Variant names:

• chr6-109499129-A-C
• rs754683982
• NM_001145128.3:c.4961T>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001145128.3(AK9):​c.4961T>G​(p.Phe1654Cys) variant causes a missense change. The variant allele was found at a frequency of 0.000000686 in 1,458,416 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. F1654S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: AK9 NM_001145128.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.91
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09384167).

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.4961T>G	p.Phe1654Cys	missense	Exon 36 of 41	NP_001138600.2	Q5TCS8-4
	ZBTB24-DT	NR_187591.1		n.1422+4561A>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AK9	ENST00000424296.7	TSL:5 MANE Select	c.4961T>G	p.Phe1654Cys	missense	Exon 36 of 41	ENSP00000410186.2	Q5TCS8-4
	AK9	ENST00000490722.1	TSL:1	c.161T>G	p.Phe54Cys	missense	Exon 2 of 7	ENSP00000419758.1	H0Y8C5
	AK9	ENST00000470564.5	TSL:5	c.1472T>G	p.Phe491Cys	missense	Exon 9 of 14	ENSP00000418771.1	H7C517

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000403 AC: 1 AN: 248334 AF XY: 0.00000745

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000884

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1458416 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 725458

African (AFR) AF: 0.00 AC: 0 AN: 33334

American (AMR) AF: 0.00 AC: 0 AN: 44190

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26098

East Asian (EAS) AF: 0.00 AC: 0 AN: 39510

South Asian (SAS) AF: 0.00 AC: 0 AN: 85502

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53380

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5754

European-Non Finnish (NFE) AF: 9.01e-7 AC: 1 AN: 1110388

Other (OTH) AF: 0.00 AC: 0 AN: 60260

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.070	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	23
DANN	Benign	0.97
DEOGEN2	Benign	0.0051	T
Eigen	Benign	-0.46
Eigen_PC	Benign	-0.44
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.57	T
M_CAP	Benign	0.033	D
MetaRNN	Benign	0.094	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.67	N
PhyloP100		3.9
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.85	N
REVEL	Benign	0.24
Sift	Benign	0.093	T
Sift4G	Uncertain	0.0050	D
Polyphen		0.0020	B
Vest4		0.27
MutPred		0.35		Loss of loop (P = 0.0203)
MVP		0.41
MPC		0.19
ClinPred		0.18	T
GERP RS		-1.1
Varity_R		0.067
gMVP		0.69
Mutation Taster		=96/4	polymorphism

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

Other links and lift over

dbSNP: rs754683982; hg19: chr6-109820332;