NM_007281.4:c.223G>T

Variant names:

• chr4-173391192-C-A
• rs149329046
• NM_007281.4:c.223G>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_007281.4(SCRG1):​c.223G>T​(p.Glu75*) variant causes a stop gained change. The variant allele was found at a frequency of 0.000000684 in 1,461,798 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SCRG1 NM_007281.4 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.07
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007281.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCRG1	NM_007281.4	MANE Select	c.223G>T	p.Glu75*	stop_gained	Exon 2 of 3	NP_009212.1	Q6FGG5
	SCRG1	NM_001329597.2		c.223G>T	p.Glu75*	stop_gained	Exon 3 of 4	NP_001316526.1	O75711

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCRG1	ENST00000296506.8	TSL:1 MANE Select	c.223G>T	p.Glu75*	stop_gained	Exon 2 of 3	ENSP00000296506.2	O75711
	SCRG1	ENST00000883955.1		c.223G>T	p.Glu75*	stop_gained	Exon 2 of 3	ENSP00000554014.1
	SCRG1	ENST00000512188.1	TSL:2	n.223G>T		non_coding_transcript_exon	Exon 7 of 9	ENSP00000425404.1	D6RD99

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461798 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727208

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53372

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111978

Other (OTH) AF: 0.00 AC: 0 AN: 60392

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.62	D
BayesDel_noAF	Pathogenic	0.65
CADD	Pathogenic	40
DANN	Uncertain	0.99
Eigen	Pathogenic	1.0
Eigen_PC	Pathogenic	0.82
FATHMM_MKL	Pathogenic	0.97	D
PhyloP100		6.1
Vest4		0.28
GERP RS		5.4
Mutation Taster		=56/144	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.18		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs149329046; hg19: chr4-174312343;