Variant chr4-173388351-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_007281.4(SCRG1):c.287A>G(p.Asn96Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000714 in 1,611,722 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000072 ( 0 hom. )

Consequence

SCRG1
NM_007281.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.32

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.10367635).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
SCRG1	NM_007281.4 linkuse as main transcript	c.287A>G	p.Asn96Ser	missense_variant	3/3	ENST00000296506.8
SCRG1	NM_001329597.2 linkuse as main transcript	c.287A>G	p.Asn96Ser	missense_variant	4/4
SCRG1	XM_047449563.1 linkuse as main transcript	c.287A>G	p.Asn96Ser	missense_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SCRG1	ENST00000296506.8 linkuse as main transcript	c.287A>G	p.Asn96Ser	missense_variant	3/3	1	NM_007281.4	P1
SCRG1	ENST00000512188.1 linkuse as main transcript	c.*306A>G		3_prime_UTR_variant, NMD_transcript_variant	9/9	2

Frequencies

GnomAD3 genomes

AF:

0.0000657

AC:

AN:

152214

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000841

AC:

AN:

249744

Hom.:

AF XY:

0.000104

AC XY:

AN XY:

135054

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:

0.000186

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000719

AC:

105

AN:

1459508

Hom.:

Cov.:

AF XY:

0.0000689

AC XY:

AN XY:

726118

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

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:

0.0000918

Gnomad4 OTH exome

AF:

0.0000332

GnomAD4 genome

AF:

0.0000657

AC:

AN:

152214

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74350

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000966

Hom.:

Bravo

AF:

0.0000491

ExAC

AF:

0.000132

AC:

EpiCase

AF:

0.0000546

EpiControl

AF:

0.000119

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 03, 2024

The c.287A>G (p.N96S) alteration is located in exon 3 (coding exon 2) of the SCRG1 gene. This alteration results from a A to G substitution at nucleotide position 287, causing the asparagine (N) at amino acid position 96 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

0.076

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.088

Eigen

Benign

-0.094

Eigen_PC

Benign

-0.0054

FATHMM_MKL

Uncertain

0.86

LIST_S2

Benign

0.72

M_CAP

Benign

0.029

MetaRNN

Benign

0.10

MetaSVM

Benign

-0.93

MutationTaster

Benign

0.93

PrimateAI

Benign

0.41

PROVEAN

Pathogenic

-4.5

REVEL

Benign

0.15

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

0.36

Vest4

0.13

MVP

0.25

MPC

0.068

ClinPred

0.84

GERP RS

3.5

Varity_R

0.70

gMVP

0.65

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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