3-121510113-G-C

Variant names:

• chr3-121510113-G-C
• rs487848
• NM_199420.4:c.1742C>G

Variant summary

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

The NM_199420.4(POLQ):​c.1742C>G​(p.Ala581Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. A581V) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: POLQ NM_199420.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.59
• Publications: 20 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POLQ	NM_199420.4	MANE Select	c.1742C>G	p.Ala581Gly	missense	Exon 11 of 30	NP_955452.3	O75417-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POLQ	ENST00000264233.6	TSL:1 MANE Select	c.1742C>G	p.Ala581Gly	missense	Exon 11 of 30	ENSP00000264233.5	O75417-1
	POLQ	ENST00000932951.1		c.1742C>G	p.Ala581Gly	missense	Exon 11 of 30	ENSP00000603010.1
	POLQ	ENST00000932953.1		c.1826C>G	p.Ala609Gly	missense	Exon 12 of 30	ENSP00000603012.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.13	T
Eigen	Benign	0.027
Eigen_PC	Benign	0.12
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.019	T
MetaRNN	Uncertain	0.56	D
MetaSVM	Benign	-0.85	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		7.6
PrimateAI	Benign	0.37	T
PROVEAN	Uncertain	-2.9	D
REVEL	Benign	0.13
Sift	Benign	0.17	T
Sift4G	Benign	0.14	T
Polyphen		0.067	B
Vest4		0.34
MutPred		0.43		Loss of helix (P = 0.0626)
MVP		0.58
MPC		0.17
ClinPred		0.88	D
GERP RS		4.0
Varity_R		0.32
gMVP		0.32
Mutation Taster		=84/16	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: rs487848; hg19: chr3-121228960;