rs669277

Variant names:

• chr3-121460823-T-C
• rs669277
• NM_199420.4:c.6968-589A>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_199420.4(POLQ):​c.6968-589A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0982 in 152,062 control chromosomes in the GnomAD database, including 1,061 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.098 (1061 hom., cov: 32)
• Consequence: POLQ NM_199420.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.152
• Publications: 2 publications found

Genes affected

POLQ (HGNC:9186): (DNA polymerase theta) Enables catalytic activity, acting on DNA; chromatin binding activity; and identical protein binding activity. Involved in DNA repair; negative regulation of double-strand break repair via homologous recombination; and protein homooligomerization. Located in Golgi apparatus; cytosol; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.192 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_199420.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POLQ	NM_199420.4	MANE Select	c.6968-589A>G		intron	N/A	NP_955452.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POLQ	ENST00000264233.6	TSL:1 MANE Select	c.6968-589A>G		intron	N/A	ENSP00000264233.5
	POLQ	ENST00000932951.1		c.6968-589A>G		intron	N/A	ENSP00000603010.1
	POLQ	ENST00000932953.1		c.6914-589A>G		intron	N/A	ENSP00000603012.1

Frequencies

GnomAD3 genomes AF: 0.0981 AC: 14910 AN: 151944 Hom.: 1056 Cov.: 32

Gnomad AFR AF: 0.195

Gnomad AMI AF: 0.0175

Gnomad AMR AF: 0.0630

Gnomad ASJ AF: 0.0787

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0112

Gnomad FIN AF: 0.0593

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0691

Gnomad OTH AF: 0.0952

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

GnomAD4 genome AF: 0.0982 AC: 14934 AN: 152062 Hom.: 1061 Cov.: 32 AF XY: 0.0953 AC XY: 7086 AN XY: 74336

African (AFR) AF: 0.195 AC: 8095 AN: 41430

American (AMR) AF: 0.0629 AC: 960 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.0787 AC: 273 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.0106 AC: 51 AN: 4822

European-Finnish (FIN) AF: 0.0593 AC: 626 AN: 10562

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.0691 AC: 4698 AN: 68000

Other (OTH) AF: 0.0942 AC: 199 AN: 2112

Alfa AF: 0.0990 Hom.: 116

Bravo AF: 0.104

Asia WGS AF: 0.0250 AC: 89 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	9.8
DANN	Benign	0.92
PhyloP100		0.15
Mutation Taster		=100/0	polymorphism (auto)

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: rs669277; hg19: chr3-121179670;