3-121467575-G-T

Position:

• chr3-121467575-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_199420.4(POLQ):​c.6911C>A​(p.Ala2304Glu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: POLQ NM_199420.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.47

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10659626).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POLQ	NM_199420.4	c.6911C>A	p.Ala2304Glu	missense_variant	24/30	ENST00000264233.6	NP_955452.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
POLQ	ENST00000264233.6	c.6911C>A	p.Ala2304Glu	missense_variant	24/30	1	NM_199420.4	ENSP00000264233	P1
POLQ	ENST00000474243.1	n.412C>A		non_coding_transcript_exon_variant	4/6	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	18
DANN	Benign	0.88
DEOGEN2	Benign	0.26	.;T
Eigen	Benign	-0.44
Eigen_PC	Benign	-0.32
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Benign	0.58	T;T
M_CAP	Benign	0.0091	T
MetaRNN	Benign	0.11	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.20	.;N
MutationTaster	Benign	1.0	P
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.22	.;N
REVEL	Benign	0.094
Sift	Benign	0.33	.;T
Sift4G	Benign	0.46	T;T
Polyphen		0.28	.;B
Vest4		0.11
MutPred		0.41		.;Gain of solvent accessibility (P = 0.0016);
MVP		0.18
MPC		0.086
ClinPred		0.29	T
GERP RS		2.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.071
gMVP		0.45

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

Other links and lift over

dbSNP: rs532411; hg19: chr3-121186422;