rs10512913

Positions:

• chr3-133820730-A-C
• chr3-133820730-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001379313.1(SRPRB):​c.*964A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.187 in 152,194 control chromosomes in the GnomAD database, including 3,506 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 0.19 (3506 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: SRPRB NM_001379313.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0350

Genes affected

SRPRB (HGNC:24085): (SRP receptor subunit beta) The protein encoded by this gene has similarity to mouse protein which is a subunit of the signal recognition particle receptor (SR). This subunit is a transmembrane GTPase belonging to the GTPase superfamily. It anchors alpha subunit, a peripheral membrane GTPase, to the ER membrane. SR is required for the cotranslational targeting of both secretory and membrane proteins to the ER membrane. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.263 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SRPRB	NM_001379313.1	c.*964A>C		3_prime_UTR_variant	7/7	ENST00000678299.1	NP_001366242.1
SRPRB	NM_021203.4	c.*964A>C		3_prime_UTR_variant	8/8		NP_067026.3
SRPRB	NR_163491.1	n.904+910A>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SRPRB	ENST00000678299.1	c.*964A>C		3_prime_UTR_variant	7/7		NM_001379313.1	ENSP00000503923	P1
SRPRB	ENST00000466490.7	c.*964A>C		3_prime_UTR_variant	8/8	5		ENSP00000418401	P1
SRPRB	ENST00000466636.1	c.*54+910A>C		intron_variant, NMD_transcript_variant		3		ENSP00000417316

Frequencies

GnomAD3 genomes AF: 0.187 AC: 28439 AN: 152078 Hom.: 3505 Cov.: 32

Gnomad AFR AF: 0.0449

Gnomad AMI AF: 0.423

Gnomad AMR AF: 0.162

Gnomad ASJ AF: 0.244

Gnomad EAS AF: 0.0427

Gnomad SAS AF: 0.0904

Gnomad FIN AF: 0.339

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.267

Gnomad OTH AF: 0.203

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.187 AC: 28432 AN: 152194 Hom.: 3506 Cov.: 32 AF XY: 0.185 AC XY: 13740 AN XY: 74388

Gnomad4 AFR AF: 0.0448

Gnomad4 AMR AF: 0.162

Gnomad4 ASJ AF: 0.244

Gnomad4 EAS AF: 0.0428

Gnomad4 SAS AF: 0.0913

Gnomad4 FIN AF: 0.339

Gnomad4 NFE AF: 0.267

Gnomad4 OTH AF: 0.200

Alfa AF: 0.243 Hom.: 6151

Bravo AF: 0.169

Asia WGS AF: 0.0670 AC: 235 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.9
DANN	Benign	0.62

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: rs10512913; hg19: chr3-133539574;