rs775980413

Variant names:

• chr22-42585900-G-A
• rs775980413
• NM_032311.5:c.1157C>T

Your query was ambiguous. Multiple possible variants found:

• chr22-42585900-G-A
• chr22-42585900-G-C
• chr22-42585900-G-T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_032311.5(POLDIP3):​c.1157C>T​(p.Ser386Phe) variant causes a missense change. The variant allele was found at a frequency of 0.000026 in 1,461,194 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S386C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000026 (0 hom.)
• Consequence: POLDIP3 NM_032311.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.13
• 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 -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.18863663).
• BS2: High AC in GnomAdExome4 at 38 AD gene.

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.1157C>T	p.Ser386Phe	missense	Exon 9 of 9	NP_115687.2
	POLDIP3	NM_001278657.2		c.1208C>T	p.Ser403Phe	missense	Exon 9 of 9	NP_001265586.1	F6VRR5
	POLDIP3	NM_178136.3		c.1070C>T	p.Ser357Phe	missense	Exon 8 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.1157C>T	p.Ser386Phe	missense	Exon 9 of 9	ENSP00000252115.5	Q9BY77-1
	POLDIP3	ENST00000348657.6	TSL:1	c.1070C>T	p.Ser357Phe	missense	Exon 8 of 8	ENSP00000252116.5	Q9BY77-2
	POLDIP3	ENST00000339677.10	TSL:1	c.451-584C>T		intron	N/A	ENSP00000343060.6	Q6R954

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000119 AC: 3 AN: 251254 AF XY: 0.0000147

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.0000992

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000260 AC: 38 AN: 1461194 Hom.: 0 Cov.: 31 AF XY: 0.0000261 AC XY: 19 AN XY: 726916

African (AFR) AF: 0.00 AC: 0 AN: 33464

American (AMR) AF: 0.00 AC: 0 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 86208

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

Middle Eastern (MID) AF: 0.000190 AC: 1 AN: 5272

European-Non Finnish (NFE) AF: 0.0000315 AC: 35 AN: 1111958

Other (OTH) AF: 0.0000332 AC: 2 AN: 60324

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000487 Hom.: 0

Bravo AF: 0.0000113

ExAC AF: 0.00000824 AC: 1

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Uncertain	0.057	T
BayesDel_noAF	Benign	-0.16
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.035	T
Eigen	Uncertain	0.28
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.0093	T
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-0.64	T
MutationAssessor	Benign	1.6	L
PhyloP100		7.1
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.21
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0050	D
Polyphen		0.98	D
Vest4		0.34
MutPred		0.32		Loss of phosphorylation at S386 (P = 0.0147)
MVP		0.43
MPC		0.016
ClinPred		0.57	D
GERP RS		4.7
Varity_R		0.17
gMVP		0.74
Mutation Taster		=77/23	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: rs775980413; hg19: chr22-42981906;