Genetic Variant DERPC:p.Thr397Pro (chr16-69119240-T-G) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001002847.4(DERPC):c.1189A>C(p.Thr397Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00646 in 702,950 control chromosomes in the GnomAD database, including 26 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0059 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0066 ( 24 hom. )

Consequence

DERPC
NM_001002847.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.25

Variant links:

Genes affected

DERPC (HGNC:54084): (DERPC proline and glycine rich nuclear protein) Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

DERPC links:

CHTF8 (HGNC:24353): (chromosome transmission fidelity factor 8) This gene encodes a short protein that forms part of the Ctf18 replication factor C (RFC) complex that occurs in both yeast and mammals. The heteroheptameric RFC complex plays a role in sister chromatid cohesion and may load the replication clamp PCNA (proliferating cell nuclear antigen) onto DNA during DNA replication and repair. This gene is ubiquitously expressed and has been shown to have reduced expression in renal and prostate tumors. Alternatively spliced transcript variants have been described. This gene has a pseudogene on chromosome X. [provided by RefSeq, Oct 2018]

CHTF8 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0045516193).

BP6

Variant 16-69119240-T-G is Benign according to our data. Variant chr16-69119240-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 2646666.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DERPC	NM_001002847.4 link	c.1189A>C	p.Thr397Pro	missense_variant	Exon 3 of 3	ENST00000519520.7	NP_001002847.1
CHTF8	NM_001039690.5 link	c.*1185A>C		3_prime_UTR_variant	Exon 4 of 4	ENST00000448552.7	NP_001034779.1	P0CG13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DERPC	ENST00000519520.7 link	c.1189A>C	p.Thr397Pro	missense_variant	Exon 3 of 3	2	NM_001002847.4	ENSP00000427718.2		P0CG12
CHTF8	ENST00000448552 link	c.*1185A>C		3_prime_UTR_variant	Exon 4 of 4	1	NM_001039690.5	ENSP00000408367.3		P0CG13

Frequencies

GnomAD3 genomes

AF:

0.00587

AC:

893

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00125

Gnomad AMI

AF:

0.00987

Gnomad AMR

AF:

0.00334

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.0153

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00894

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00459

AC:

640

AN:

139474

Hom.:

AF XY:

0.00476

AC XY:

360

AN XY:

75612

show subpopulations

Gnomad AFR exome

AF:

0.000466

Gnomad AMR exome

AF:

0.00143

Gnomad ASJ exome

AF:

0.000481

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00142

Gnomad FIN exome

AF:

0.0124

Gnomad NFE exome

AF:

0.00815

Gnomad OTH exome

AF:

0.00546

GnomAD4 exome

AF:

0.00662

AC:

3647

AN:

550636

Hom.:

Cov.:

AF XY:

0.00678

AC XY:

2022

AN XY:

298088

show subpopulations

Gnomad4 AFR exome

AF:

0.000949

Gnomad4 AMR exome

AF:

0.00213

Gnomad4 ASJ exome

AF:

0.0000999

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00127

Gnomad4 FIN exome

AF:

0.0137

Gnomad4 NFE exome

AF:

0.00902

Gnomad4 OTH exome

AF:

0.00497

GnomAD4 genome

AF:

0.00586

AC:

893

AN:

152314

Hom.:

Cov.:

AF XY:

0.00549

AC XY:

409

AN XY:

74494

show subpopulations

Gnomad4 AFR

AF:

0.00125

Gnomad4 AMR

AF:

0.00333

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00124

Gnomad4 FIN

AF:

0.0153

Gnomad4 NFE

AF:

0.00894

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.00556

Hom.:

Bravo

AF:

0.00446

TwinsUK

AF:

0.00405

AC:

ALSPAC

AF:

0.00519

AC:

ExAC

AF:

0.00393

AC:

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Feb 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

CHTF8: BS2; DERPC: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.34

CADD

Benign

DANN

Benign

0.76

DEOGEN2

Benign

0.0093

Eigen

Benign

-0.67

Eigen_PC

Benign

-0.58

FATHMM_MKL

Benign

0.16

LIST_S2

Benign

0.30

MetaRNN

Benign

0.0046

MetaSVM

Benign

-1.0

PrimateAI

Benign

0.43

PROVEAN

Benign

-0.14

REVEL

Benign

0.030

Sift

Benign

0.042

Sift4G

Benign

0.17

Polyphen

0.018

Vest4

0.14

MVP

0.44

ClinPred

0.0074

GERP RS

3.0

Varity_R

0.069

gMVP

0.14

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over