Variant 4-173388347-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_007281.4(SCRG1):c.291T>G(p.Asn97Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000434 in 1,611,124 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

SCRG1
NM_007281.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.962

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 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=0.026615977).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
SCRG1	NM_007281.4 linkuse as main transcript	c.291T>G	p.Asn97Lys	missense_variant	3/3	ENST00000296506.8
SCRG1	NM_001329597.2 linkuse as main transcript	c.291T>G	p.Asn97Lys	missense_variant	4/4
SCRG1	XM_047449563.1 linkuse as main transcript	c.291T>G	p.Asn97Lys	missense_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SCRG1	ENST00000296506.8 linkuse as main transcript	c.291T>G	p.Asn97Lys	missense_variant	3/3	1	NM_007281.4	P1
SCRG1	ENST00000512188.1 linkuse as main transcript	c.*310T>G		3_prime_UTR_variant, NMD_transcript_variant	9/9	2

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152210

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:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000411

AC:

AN:

1458914

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

725880

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:

0.0000349

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000498

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152210

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74352

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:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

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

Nov 14, 2023

The c.291T>G (p.N97K) alteration is located in exon 3 (coding exon 2) of the SCRG1 gene. This alteration results from a T to G substitution at nucleotide position 291, causing the asparagine (N) at amino acid position 97 to be replaced by a lysine (K). 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

0.078

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.69

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.020

Eigen

Benign

-0.85

Eigen_PC

Benign

-0.87

FATHMM_MKL

Benign

0.092

LIST_S2

Benign

0.48

M_CAP

Benign

0.0043

MetaRNN

Benign

0.027

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

PrimateAI

Benign

0.38

PROVEAN

Benign

-1.4

REVEL

Benign

0.018

Sift

Benign

0.052

Sift4G

Benign

0.22

Polyphen

0.0

Vest4

0.12

MutPred

0.29

Gain of methylation at N97 (P = 0.001);

MVP

0.15

MPC

0.11

ClinPred

0.16

GERP RS

0.043

Varity_R

0.071

gMVP

0.39

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