Variant 4-173391291-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_007281.4(SCRG1):c.124C>T(p.Pro42Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000479 in 1,461,882 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P42L) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

SCRG1
NM_007281.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.63

Variant links:

Genes affected

SCRG1 (HGNC:17036): (stimulator of chondrogenesis 1) Scrapie-responsive gene 1 is associated with neurodegenerative changes observed in transmissible spongiform encephalopathies. It may play a role in host response to prion-associated infections. The scrapie responsive protein 1 may be partly included in the membrane or secreted by the cells due to its hydrophobic N-terminus. In addition, the encoded protein can interact with bone marrow stromal cell antigen 1 (BST1) to enhance the differentiation potentials of human mesenchymal stem cells during tissue and bone regeneration. [provided by RefSeq, Jul 2016]

SCRG1 links:

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ACMG classification

Classification made for transcript

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=0.38580775).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
SCRG1	NM_007281.4 linkuse as main transcript	c.124C>T	p.Pro42Ser	missense_variant	2/3	ENST00000296506.8
SCRG1	NM_001329597.2 linkuse as main transcript	c.124C>T	p.Pro42Ser	missense_variant	3/4
SCRG1	XM_047449563.1 linkuse as main transcript	c.124C>T	p.Pro42Ser	missense_variant	3/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SCRG1	ENST00000296506.8 linkuse as main transcript	c.124C>T	p.Pro42Ser	missense_variant	2/3	1	NM_007281.4	P1
SCRG1	ENST00000512188.1 linkuse as main transcript	c.124C>T	p.Pro42Ser	missense_variant, NMD_transcript_variant	7/9	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000159

AC:

AN:

251408

Hom.:

AF XY:

0.0000294

AC XY:

AN XY:

135872

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:

0.0000980

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000880

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000479

AC:

AN:

1461882

Hom.:

Cov.:

AF XY:

0.00000963

AC XY:

AN XY:

727240

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:

0.0000696

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Alfa

AF:

0.000111

Hom.:

ExAC

AF:

0.0000165

AC:

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

Jan 30, 2024

The c.124C>T (p.P42S) alteration is located in exon 2 (coding exon 1) of the SCRG1 gene. This alteration results from a C to T substitution at nucleotide position 124, causing the proline (P) at amino acid position 42 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

Benign

0.18

BayesDel_addAF

Uncertain

0.017

BayesDel_noAF

Uncertain

-0.010

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.13

Eigen

Uncertain

0.67

Eigen_PC

Pathogenic

0.67

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.74

M_CAP

Benign

0.055

MetaRNN

Benign

0.39

MetaSVM

Uncertain

-0.098

MutationTaster

Benign

1.0

PrimateAI

Benign

0.38

PROVEAN

Pathogenic

-8.0

REVEL

Uncertain

0.39

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.23

MutPred

0.31

Gain of relative solvent accessibility (P = 0.1571);

MVP

0.66

MPC

0.43

ClinPred

0.99

GERP RS

5.5

Varity_R

0.85

gMVP

0.74

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