NM_032311.5:c.702T>C

Variant names:

• chr22-42596297-A-G
• rs369338847
• NM_032311.5:c.702T>C

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_032311.5(POLDIP3):​c.702T>C​(p.Asp234Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,814 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: POLDIP3 NM_032311.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.648
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (REVEL=0.056).
• BP7: Synonymous conserved (PhyloP=0.648 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032311.5. 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
	POLDIP3	NM_032311.5	MANE Select	c.702T>C	p.Asp234Asp	synonymous	Exon 5 of 9	NP_115687.2
	POLDIP3	NM_001278657.2		c.753T>C	p.Asp251Asp	synonymous	Exon 5 of 9	NP_001265586.1	F6VRR5
	POLDIP3	NM_178136.3		c.615T>C	p.Asp205Asp	synonymous	Exon 4 of 8	NP_835237.1	Q9BY77-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POLDIP3	ENST00000252115.10	TSL:1 MANE Select	c.702T>C	p.Asp234Asp	synonymous	Exon 5 of 9	ENSP00000252115.5	Q9BY77-1
	POLDIP3	ENST00000348657.6	TSL:1	c.615T>C	p.Asp205Asp	synonymous	Exon 4 of 8	ENSP00000252116.5	Q9BY77-2
	POLDIP3	ENST00000339677.10	TSL:1	c.450+6473T>C		intron	N/A	ENSP00000343060.6	Q6R954

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461814 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727222

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111938

Other (OTH) AF: 0.00 AC: 0 AN: 60394

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	3.3
DANN	Benign	0.57
PhyloP100		0.65

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: rs369338847; hg19: chr22-42992303;