22-42596290-T-A

Variant names:

• chr22-42596290-T-A
• NM_032311.5:c.709A>T

Variant summary

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

The NM_032311.5(POLDIP3):​c.709A>T​(p.Thr237Ser) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: POLDIP3 NM_032311.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.54

Genes affected

POLDIP3 (HGNC:23782): (DNA polymerase delta interacting protein 3) This gene encodes an RRM (RNA recognition motif)-containing protein that participates in the regulation of translation by recruiting ribosomal protein S6 kinase beta-1 to mRNAs. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]

ENSG00000289517 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POLDIP3	NM_032311.5	c.709A>T	p.Thr237Ser	missense_variant	Exon 5 of 9	ENST00000252115.10	NP_115687.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POLDIP3	ENST00000252115.10	c.709A>T	p.Thr237Ser	missense_variant	Exon 5 of 9	1	NM_032311.5	ENSP00000252115.5
ENSG00000289517	ENST00000617178.5	n.*1570A>T		non_coding_transcript_exon_variant	Exon 10 of 14	1		ENSP00000482500.2
ENSG00000289517	ENST00000617178.5	n.*1570A>T		3_prime_UTR_variant	Exon 10 of 14	1		ENSP00000482500.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jun 23, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.709A>T (p.T237S) alteration is located in exon 5 (coding exon 5) of the POLDIP3 gene. This alteration results from a A to T substitution at nucleotide position 709, causing the threonine (T) at amino acid position 237 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Uncertain	0.039	T
BayesDel_noAF	Benign	-0.18
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0062	.;T;T;T
Eigen	Uncertain	0.50
Eigen_PC	Uncertain	0.48
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.86	D;D;T;D
M_CAP	Benign	0.0078	T
MetaRNN	Benign	0.29	T;T;T;T
MetaSVM	Benign	-0.59	T
MutationAssessor	Uncertain	2.5	.;M;.;.
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-0.67	N;N;.;.
REVEL	Benign	0.17
Sift	Benign	0.16	T;D;.;.
Sift4G	Uncertain	0.026	D;D;D;D
Polyphen		1.0	D;D;.;.
Vest4		0.60
MutPred		0.38		.;Loss of sheet (P = 0.0126);.;.;
MVP		0.58
MPC		0.21
ClinPred		0.80	D
GERP RS		4.8
Varity_R		0.14
gMVP		0.33

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.28		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.28		Position offset: -37

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: chr22-42992296;