4-173391326-C-T

Position:

• chr4-173391326-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_007281.4(SCRG1):​c.89G>A​(p.Arg30Lys) 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. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SCRG1 NM_007281.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.98

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]

ACMG classification

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=0.08111867).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SCRG1	NM_007281.4	c.89G>A	p.Arg30Lys	missense_variant	2/3	ENST00000296506.8
SCRG1	NM_001329597.2	c.89G>A	p.Arg30Lys	missense_variant	3/4
SCRG1	XM_047449563.1	c.89G>A	p.Arg30Lys	missense_variant	3/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SCRG1	ENST00000296506.8	c.89G>A	p.Arg30Lys	missense_variant	2/3	1	NM_007281.4	P1
SCRG1	ENST00000512188.1	c.89G>A	p.Arg30Lys	missense_variant, NMD_transcript_variant	7/9	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251416 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135874

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.091
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	17
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0062	T
Eigen	Benign	-0.21
Eigen_PC	Benign	-0.036
FATHMM_MKL	Benign	0.58	D
LIST_S2	Benign	0.62	T
M_CAP	Benign	0.0017	T
MetaRNN	Benign	0.081	T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	0.94	N
PrimateAI	Benign	0.37	T
PROVEAN	Benign	0.080	N
REVEL	Benign	0.020
Sift	Benign	0.45	T
Sift4G	Benign	0.77	T
Polyphen		0.0010	B
Vest4		0.13
MutPred		0.20		Gain of methylation at R30 (P = 0.0276);
MVP		0.34
MPC		0.075
ClinPred		0.77	D
GERP RS		4.7
Varity_R		0.092
gMVP		0.53

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs764595661; hg19: chr4-174312477;