8-119855735-C-G

Position:

• chr8-119855735-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_024094.3(DSCC1):​c.61G>C​(p.Glu21Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000211 in 1,423,652 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 (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: DSCC1 NM_024094.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.45

Genes affected

DSCC1 (HGNC:24453): (DNA replication and sister chromatid cohesion 1) CHTF18 (MIM 613201), CHTF8 (MIM 613202), and DSCC1 are components of an alternative replication factor C (RFC) (see MIM 600404) complex that loads PCNA (MIM 176740) onto DNA during S phase of the cell cycle (Merkle et al., 2003 [PubMed 12766176]; Bermudez et al., 2003 [PubMed 12930902]).[supplied by OMIM, Dec 2009]

DSCC1 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.27227193).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DSCC1	NM_024094.3	c.61G>C	p.Glu21Gln	missense_variant	1/9	ENST00000313655.5	NP_076999.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DSCC1	ENST00000313655.5	c.61G>C	p.Glu21Gln	missense_variant	1/9	1	NM_024094.3	ENSP00000322180.4
DSCC1	ENST00000521795.1	n.124G>C		non_coding_transcript_exon_variant	1/2	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000211 AC: 3 AN: 1423652 Hom.: 0 Cov.: 31 AF XY: 0.00000284 AC XY: 2 AN XY: 705122

Gnomad4 AFR exome AF: 0.0000633

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000171

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000509 Hom.: 0

ExAC AF: 0.00000837 AC: 1

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

Sep 27, 2021

The c.61G>C (p.E21Q) alteration is located in exon 1 (coding exon 1) of the DSCC1 gene. This alteration results from a G to C substitution at nucleotide position 61, causing the glutamic acid (E) at amino acid position 21 to be replaced by a glutamine (Q). 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	0.20
BayesDel_addAF	Benign	-0.095	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.068	T
Eigen	Uncertain	0.45
Eigen_PC	Uncertain	0.47
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.046	D
MetaRNN	Benign	0.27	T
MetaSVM	Benign	-0.85	T
MutationAssessor	Uncertain	2.6	M
PrimateAI	Pathogenic	0.79	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.11
Sift	Uncertain	0.017	D
Sift4G	Uncertain	0.034	D
Polyphen		0.91	P
Vest4		0.16
MutPred		0.34		Loss of ubiquitination at K16 (P = 0.0777);
MVP		0.52
MPC		0.78
ClinPred		0.98	D
GERP RS		4.8
Varity_R		0.38
gMVP		0.45

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

Other links and lift over

dbSNP: rs1554668606; hg19: chr8-120867975;