rs758762868

Variant names:

• chr12-132635906-T-A
• NM_006231.4:c.5797A>T

Your query was ambiguous. Multiple possible variants found:

• chr12-132635906-T-A
• chr12-132635906-T-C
• chr12-132635906-T-G

Variant summary

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

The NM_006231.4(POLE):​c.5797A>T​(p.Ile1933Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 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: 33)
• Consequence: POLE NM_006231.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.187

Genes affected

POLE (HGNC:9177): (DNA polymerase epsilon, catalytic subunit) This gene encodes the catalytic subunit of DNA polymerase epsilon. The enzyme is involved in DNA repair and chromosomal DNA replication. Mutations in this gene have been associated with colorectal cancer 12 and facial dysmorphism, immunodeficiency, livedo, and short stature. [provided by RefSeq, Sep 2013]

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=0.09735924).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POLE	NM_006231.4	c.5797A>T	p.Ile1933Phe	missense_variant	Exon 42 of 49	ENST00000320574.10	NP_006222.2
POLE	XM_011534795.4	c.5797A>T	p.Ile1933Phe	missense_variant	Exon 42 of 48		XP_011533097.1
POLE	XM_011534797.4	c.4876A>T	p.Ile1626Phe	missense_variant	Exon 34 of 40		XP_011533099.1
POLE	XM_011534802.4	c.2785A>T	p.Ile929Phe	missense_variant	Exon 18 of 24		XP_011533104.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POLE	ENST00000320574.10	c.5797A>T	p.Ile1933Phe	missense_variant	Exon 42 of 49	1	NM_006231.4	ENSP00000322570.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.080
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	0.70
DANN	Benign	0.67
DEOGEN2	Benign	0.073	T;.
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.32	N
LIST_S2	Uncertain	0.88	D;D
M_CAP	Benign	0.0066	T
MetaRNN	Benign	0.097	T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.97	L;.
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-1.6	N;N
REVEL	Benign	0.034
Sift	Uncertain	0.021	D;D
Sift4G	Uncertain	0.032	D;D
Polyphen		0.041	B;.
Vest4		0.27
MutPred		0.55		Gain of catalytic residue at R1932 (P = 0);.;
MVP		0.055
MPC		0.31
ClinPred		0.19	T
GERP RS		-4.3
Varity_R		0.059
gMVP		0.31

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-133212492;