rs7222251

Variant names:

• chr17-2322822-T-C
• rs7222251
• NM_018128.5:c.*1374A>G

Variant summary

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

The NM_018128.5(TSR1):​c.*1374A>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 0.27 in 340,168 control chromosomes in the GnomAD database, including 13,081 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 0.29 (6288 hom., cov: 31)
  • Exomes 𝑓: 0.26 (6793 hom.)
• Consequence: TSR1 NM_018128.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.206

Genes affected

TSR1 (HGNC:25542): (TSR1 ribosome maturation factor) Enables RNA binding activity. Predicted to be involved in endonucleolytic cleavage of tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) and maturation of SSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA). Predicted to be located in nucleolus. Predicted to be part of preribosome, small subunit precursor. [provided by Alliance of Genome Resources, Apr 2022]

SRR (HGNC:14398): (serine racemase) Enables several functions, including L-serine ammonia-lyase activity; PDZ domain binding activity; and anion binding activity. Involved in pyruvate biosynthetic process; response to lipopolysaccharide; and serine family amino acid metabolic process. Located in cytoplasm and neuronal cell body. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.351 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TSR1	NM_018128.5	c.*1374A>G		3_prime_UTR_variant	Exon 15 of 15	ENST00000301364.10	NP_060598.3
SRR	NM_021947.3	c.595-314T>C		intron_variant	Intron 6 of 7	ENST00000344595.10	NP_068766.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TSR1	ENST00000301364	c.*1374A>G		3_prime_UTR_variant	Exon 15 of 15	1	NM_018128.5	ENSP00000301364.4
SRR	ENST00000344595.10	c.595-314T>C		intron_variant	Intron 6 of 7	1	NM_021947.3	ENSP00000339435.5

Frequencies

GnomAD3 genomes AF: 0.287 AC: 43576 AN: 151688 Hom.: 6280 Cov.: 31

Gnomad AFR AF: 0.322

Gnomad AMI AF: 0.194

Gnomad AMR AF: 0.359

Gnomad ASJ AF: 0.256

Gnomad EAS AF: 0.228

Gnomad SAS AF: 0.187

Gnomad FIN AF: 0.221

Gnomad MID AF: 0.248

Gnomad NFE AF: 0.275

Gnomad OTH AF: 0.309

GnomAD4 exome AF: 0.257 AC: 48394 AN: 188362 Hom.: 6793 Cov.: 0 AF XY: 0.249 AC XY: 25359 AN XY: 101964

Gnomad4 AFR exome AF: 0.324

Gnomad4 AMR exome AF: 0.394

Gnomad4 ASJ exome AF: 0.263

Gnomad4 EAS exome AF: 0.220

Gnomad4 SAS exome AF: 0.177

Gnomad4 FIN exome AF: 0.232

Gnomad4 NFE exome AF: 0.271

Gnomad4 OTH exome AF: 0.268

GnomAD4 genome AF: 0.287 AC: 43604 AN: 151806 Hom.: 6288 Cov.: 31 AF XY: 0.284 AC XY: 21081 AN XY: 74192

Gnomad4 AFR AF: 0.322

Gnomad4 AMR AF: 0.359

Gnomad4 ASJ AF: 0.256

Gnomad4 EAS AF: 0.227

Gnomad4 SAS AF: 0.187

Gnomad4 FIN AF: 0.221

Gnomad4 NFE AF: 0.275

Gnomad4 OTH AF: 0.308

Alfa AF: 0.288 Hom.: 800

Bravo AF: 0.301

Asia WGS AF: 0.232 AC: 808 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.1
DANN	Benign	0.55

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: rs7222251; hg19: chr17-2226116;