16-69120590-C-G

Position:

• chr16-69120590-C-G

Variant summary

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

The NM_001039690.5(CHTF8):​c.201G>C​(p.Glu67Asp) 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: CHTF8 NM_001039690.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.29

Genes affected

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]

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

CHTF8 (HGNC:):

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=0.23282245).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHTF8	NM_001039690.5	c.201G>C	p.Glu67Asp	missense_variant	4/4	ENST00000448552.7	NP_001034779.1
DERPC	NM_001002847.4	c.-162G>C		5_prime_UTR_variant	3/3	ENST00000519520.7	NP_001002847.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHTF8	ENST00000448552.7	c.201G>C	p.Glu67Asp	missense_variant	4/4	1	NM_001039690.5	ENSP00000408367.3
DERPC	ENST00000519520.7	c.-162G>C		5_prime_UTR_variant	3/3	2	NM_001002847.4	ENSP00000427718.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.0000189

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 03, 2023

The c.201G>C (p.E67D) alteration is located in exon 4 (coding exon 3) of the CHTF8 gene. This alteration results from a G to C substitution at nucleotide position 201, causing the glutamic acid (E) at amino acid position 67 to be replaced by an aspartic acid (D). 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	0.21
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.070
CADD	Benign	21
DANN	Benign	0.93
DEOGEN2	Benign	0.027	T;T
Eigen	Uncertain	0.28
Eigen_PC	Uncertain	0.39
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.85	.;T
M_CAP	Benign	0.0048	T
MetaRNN	Benign	0.23	T;T
MetaSVM	Benign	-0.77	T
MutationAssessor	Benign	0.93	L;L
MutationTaster	Benign	1.0	D;D;D;D;D;D;D;D
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-0.75	N;N
REVEL	Benign	0.077
Sift	Benign	0.52	T;T
Sift4G	Benign	0.55	T;T
Polyphen		0.13	B;B
Vest4		0.29
MutPred		0.47		Gain of loop (P = 0.0435);Gain of loop (P = 0.0435);
MVP		0.52
MPC		0.33
ClinPred		0.36	T
GERP RS		5.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
gMVP		0.39

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.18		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

Other links and lift over

dbSNP: rs1961576802; hg19: chr16-69154493;