rs2292152

Positions:

• chr5-65669951-T-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_019072.3(SGTB):​c.*295A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0335 in 259,270 control chromosomes in the GnomAD database, including 249 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.035 (152 hom., cov: 33)
  • Exomes 𝑓: 0.031 (97 hom.)
• Consequence: SGTB NM_019072.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.32

Genes affected

SGTB (HGNC:23567): (small glutamine rich tetratricopeptide repeat co-chaperone beta) Predicted to enable molecular adaptor activity. Predicted to be involved in positive regulation of chaperone-mediated protein folding; posttranslational protein targeting to endoplasmic reticulum membrane; and ubiquitin-dependent ERAD pathway. Predicted to be part of TRC complex. Predicted to be active in membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.23).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0822 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SGTB	NM_019072.3	c.*295A>G		3_prime_UTR_variant	11/11	ENST00000381007.9	NP_061945.1
SGTB	XM_005248548.4	c.*295A>G		3_prime_UTR_variant	11/11		XP_005248605.1
SGTB	XM_047417334.1	c.*295A>G		3_prime_UTR_variant	10/10		XP_047273290.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SGTB	ENST00000381007	c.*295A>G		3_prime_UTR_variant	11/11	1	NM_019072.3	ENSP00000370395.4

Frequencies

GnomAD3 genomes AF: 0.0349 AC: 5316 AN: 152212 Hom.: 149 Cov.: 33

Gnomad AFR AF: 0.0497

Gnomad AMI AF: 0.0406

Gnomad AMR AF: 0.0321

Gnomad ASJ AF: 0.0637

Gnomad EAS AF: 0.0864

Gnomad SAS AF: 0.0897

Gnomad FIN AF: 0.00160

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0219

Gnomad OTH AF: 0.0431

GnomAD4 exome AF: 0.0313 AC: 3352 AN: 106940 Hom.: 97 Cov.: 0 AF XY: 0.0327 AC XY: 1817 AN XY: 55588

Gnomad4 AFR exome AF: 0.0546

Gnomad4 AMR exome AF: 0.0256

Gnomad4 ASJ exome AF: 0.0678

Gnomad4 EAS exome AF: 0.0827

Gnomad4 SAS exome AF: 0.0811

Gnomad4 FIN exome AF: 0.00243

Gnomad4 NFE exome AF: 0.0206

Gnomad4 OTH exome AF: 0.0403

GnomAD4 genome AF: 0.0350 AC: 5334 AN: 152330 Hom.: 152 Cov.: 33 AF XY: 0.0357 AC XY: 2660 AN XY: 74512

Gnomad4 AFR AF: 0.0500

Gnomad4 AMR AF: 0.0321

Gnomad4 ASJ AF: 0.0637

Gnomad4 EAS AF: 0.0862

Gnomad4 SAS AF: 0.0892

Gnomad4 FIN AF: 0.00160

Gnomad4 NFE AF: 0.0219

Gnomad4 OTH AF: 0.0460

Alfa AF: 0.0243 Hom.: 30

Bravo AF: 0.0367

Asia WGS AF: 0.117 AC: 406 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.23
CADD	Benign	16
DANN	Benign	0.86

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

Other links and lift over

dbSNP: rs2292152; hg19: chr5-64965778;