8-119855707-C-G

Position:

• chr8-119855707-C-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_024094.3(DSCC1):​c.89G>C​(p.Gly30Ala) 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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: DSCC1 NM_024094.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.399

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.059253544).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DSCC1	NM_024094.3	c.89G>C	p.Gly30Ala	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.89G>C	p.Gly30Ala	missense_variant	1/9	1	NM_024094.3	ENSP00000322180.4
DSCC1	ENST00000521795.1	n.152G>C		non_coding_transcript_exon_variant	1/2	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000756

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

May 24, 2024

The c.89G>C (p.G30A) 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 89, causing the glycine (G) at amino acid position 30 to be replaced by an alanine (A). 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	0.067
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	11
DANN	Benign	0.85
DEOGEN2	Benign	0.026	T
Eigen	Benign	-0.76
Eigen_PC	Benign	-0.60
FATHMM_MKL	Benign	0.20	N
LIST_S2	Benign	0.61	T
M_CAP	Benign	0.0086	T
MetaRNN	Benign	0.059	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.41	N
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	0.64	N
REVEL	Benign	0.042
Sift	Benign	0.58	T
Sift4G	Benign	0.34	T
Polyphen		0.0	B
Vest4		0.063
MutPred		0.33		Gain of sheet (P = 0.0344);
MVP		0.099
MPC		0.27
ClinPred		0.086	T
GERP RS		1.9
Varity_R		0.042
gMVP		0.20

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: rs867858865; hg19: chr8-120867947;