16-69120529-G-T

Variant names:

• chr16-69120529-G-T
• rs375674216
• NM_001039690.5:c.262C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001039690.5(CHTF8):​c.262C>A​(p.Arg88Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/20 in silico tools predict 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. R88H) has been classified 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: 0.107
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04347235).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001039690.5. 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
	CHTF8	NM_001039690.5	MANE Select	c.262C>A	p.Arg88Ser	missense	Exon 4 of 4	NP_001034779.1	P0CG13
	DERPC	NM_001002847.4	MANE Select	c.-101C>A		5_prime_UTR	Exon 3 of 3	NP_001002847.1	P0CG12
	CHTF8	NM_001040146.5		c.262C>A	p.Arg88Ser	missense	Exon 4 of 4	NP_001035236.1	P0CG13

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHTF8	ENST00000448552.7	TSL:1 MANE Select	c.262C>A	p.Arg88Ser	missense	Exon 4 of 4	ENSP00000408367.3	P0CG13
	DERPC	ENST00000519520.7	TSL:2 MANE Select	c.-101C>A		5_prime_UTR	Exon 3 of 3	ENSP00000427718.2	P0CG12
	CHTF8	ENST00000398235.6	TSL:2	c.262C>A	p.Arg88Ser	missense	Exon 4 of 4	ENSP00000381290.2	P0CG13

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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	0.11
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	0.61
DANN	Benign	0.59
DEOGEN2	Benign	0.015	T
Eigen	Benign	-1.9
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.075	N
LIST_S2	Benign	0.21	T
M_CAP	Benign	0.0029	T
MetaRNN	Benign	0.043	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	-0.69	N
PhyloP100		0.11
PrimateAI	Benign	0.22	T
PROVEAN	Benign	0.55	N
REVEL	Benign	0.038
Sift	Benign	0.98	T
Sift4G	Benign	0.73	T
Polyphen		0.0	B
Vest4		0.042
MutPred		0.43		Loss of solvent accessibility (P = 0.0238)
MVP		0.34
MPC		0.27
ClinPred		0.036	T
GERP RS		-7.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
gMVP		0.22

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: rs375674216; hg19: chr16-69154432;