Variant chr8-119853160-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_024094.3(DSCC1):c.238A>T(p.Thr80Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000164 in 1,461,836 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

DSCC1
NM_024094.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.51

Variant links:

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 links:

DSCC1 (HGNC:):

DSCC1 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.969

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DSCC1	NM_024094.3 linkuse as main transcript	c.238A>T	p.Thr80Ser	missense_variant	2/9	ENST00000313655.5	NP_076999.2	Q9BVC3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
DSCC1	ENST00000313655.5 linkuse as main transcript	c.238A>T	p.Thr80Ser	missense_variant	2/9	1	NM_024094.3	ENSP00000322180.4	Q9BVC3
DSCC1	ENST00000521795.1 linkuse as main transcript	n.301A>T		non_coding_transcript_exon_variant	2/2	2
ENSG00000286362	ENST00000665858.1 linkuse as main transcript	n.203-1515T>A		intron_variant

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000796

AC:

AN:

251414

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135876

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000164

AC:

AN:

1461836

Hom.:

Cov.:

AF XY:

0.0000124

AC XY:

AN XY:

727226

show subpopulations

Gnomad4 AFR exome

AF:

0.00

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:

0.0000207

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000282

Hom.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 28, 2023

The c.238A>T (p.T80S) alteration is located in exon 2 (coding exon 2) of the DSCC1 gene. This alteration results from a A to T substitution at nucleotide position 238, causing the threonine (T) at amino acid position 80 to be replaced by a serine (S). 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

Uncertain

0.37

BayesDel_addAF

Pathogenic

0.37

BayesDel_noAF

Pathogenic

0.31

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.27

Eigen

Uncertain

0.66

Eigen_PC

Uncertain

0.61

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.82

M_CAP

Benign

0.074

MetaRNN

Pathogenic

0.97

MetaSVM

Uncertain

0.091

MutationAssessor

Uncertain

2.4

PrimateAI

Uncertain

0.63

PROVEAN

Uncertain

-3.0

REVEL

Pathogenic

0.77

Sift

Pathogenic

0.0

Sift4G

Benign

0.13

Polyphen

1.0

Vest4

0.94

MutPred

0.87

Gain of relative solvent accessibility (P = 0.0479);

MVP

0.88

MPC

0.83

ClinPred

0.98

GERP RS

4.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.65

gMVP

0.63

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