22-50529836-T-G

Position:

• chr22-50529836-T-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000487577.5(TYMP):​c.-127A>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00932 in 882,600 control chromosomes in the GnomAD database, including 461 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.034 (304 hom., cov: 33)
  • Exomes 𝑓: 0.0041 (157 hom.)
• Consequence: TYMP ENST00000487577.5 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.47

Genes affected

TYMP (HGNC:3148): (thymidine phosphorylase) This gene encodes an angiogenic factor which promotes angiogenesis in vivo and stimulates the in vitro growth of a variety of endothelial cells. It has a highly restricted target cell specificity acting only on endothelial cells. Mutations in this gene have been associated with mitochondrial neurogastrointestinal encephalomyopathy. Multiple alternatively spliced transcript variants have been identified. [provided by RefSeq, Apr 2012]

CIMAP1B (HGNC:34388): (ciliary microtubule associated protein 1B) Predicted to be active in cytoskeleton. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BP6: Variant 22-50529836-T-G is Benign according to our data. Variant chr22-50529836-T-G is described in ClinVar as [Benign]. Clinvar id is 1294147.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.117 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TYMP	NM_001953.5	c.-11+68A>C		intron_variant		ENST00000252029.8	NP_001944.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TYMP	ENST00000252029.8	c.-11+68A>C		intron_variant		1	NM_001953.5	ENSP00000252029	P2

Frequencies

GnomAD3 genomes AF: 0.0344 AC: 5229 AN: 152132 Hom.: 302 Cov.: 33

Gnomad AFR AF: 0.119

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0131

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000397

Gnomad OTH AF: 0.0206

GnomAD4 exome AF: 0.00408 AC: 2980 AN: 730354 Hom.: 157 Cov.: 10 AF XY: 0.00344 AC XY: 1280 AN XY: 371692

Gnomad4 AFR exome AF: 0.127

Gnomad4 AMR exome AF: 0.00971

Gnomad4 ASJ exome AF: 0.000871

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000204

Gnomad4 FIN exome AF: 0.0000318

Gnomad4 NFE exome AF: 0.000289

Gnomad4 OTH exome AF: 0.00860

GnomAD4 genome AF: 0.0344 AC: 5244 AN: 152246 Hom.: 304 Cov.: 33 AF XY: 0.0328 AC XY: 2444 AN XY: 74436

Gnomad4 AFR AF: 0.119

Gnomad4 AMR AF: 0.0131

Gnomad4 ASJ AF: 0.00144

Gnomad4 EAS AF: 0.000194

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000397

Gnomad4 OTH AF: 0.0203

Alfa AF: 0.0257 Hom.: 25

Bravo AF: 0.0396

Asia WGS AF: 0.00577 AC: 20 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 07, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	1.2
DANN	Benign	0.69

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: rs115930767; hg19: chr22-50968265;