NM_001953.5:c.516+27A>G

Variant names:

• chr22-50528485-T-C
• rs470119
• NM_001953.5:c.516+27A>G

Variant summary

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

The NM_001953.5(TYMP):​c.516+27A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.606 in 1,590,248 control chromosomes in the GnomAD database, including 296,084 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.55 (24204 hom., cov: 32)
  • Exomes 𝑓: 0.61 (271880 hom.)
• Consequence: TYMP NM_001953.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.821

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 22-50528485-T-C is Benign according to our data. Variant chr22-50528485-T-C is described in ClinVar as [Benign]. Clinvar id is 671618.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.691 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TYMP	NM_001953.5	c.516+27A>G		intron_variant	Intron 4 of 9	ENST00000252029.8	NP_001944.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TYMP	ENST00000252029.8	c.516+27A>G		intron_variant	Intron 4 of 9	1	NM_001953.5	ENSP00000252029.3

Frequencies

GnomAD3 genomes AF: 0.551 AC: 83688 AN: 151942 Hom.: 24209 Cov.: 32

Gnomad AFR AF: 0.361

Gnomad AMI AF: 0.596

Gnomad AMR AF: 0.617

Gnomad ASJ AF: 0.662

Gnomad EAS AF: 0.710

Gnomad SAS AF: 0.665

Gnomad FIN AF: 0.660

Gnomad MID AF: 0.718

Gnomad NFE AF: 0.607

Gnomad OTH AF: 0.560

GnomAD3 exomes AF: 0.615 AC: 149977 AN: 243934 Hom.: 46680 AF XY: 0.621 AC XY: 81973 AN XY: 131934

Gnomad AFR exome AF: 0.348

Gnomad AMR exome AF: 0.626

Gnomad ASJ exome AF: 0.641

Gnomad EAS exome AF: 0.697

Gnomad SAS exome AF: 0.676

Gnomad FIN exome AF: 0.654

Gnomad NFE exome AF: 0.608

Gnomad OTH exome AF: 0.627

GnomAD4 exome AF: 0.612 AC: 880749 AN: 1438188 Hom.: 271880 Cov.: 25 AF XY: 0.615 AC XY: 440451 AN XY: 716548

Gnomad4 AFR exome AF: 0.346

Gnomad4 AMR exome AF: 0.630

Gnomad4 ASJ exome AF: 0.645

Gnomad4 EAS exome AF: 0.718

Gnomad4 SAS exome AF: 0.677

Gnomad4 FIN exome AF: 0.644

Gnomad4 NFE exome AF: 0.609

Gnomad4 OTH exome AF: 0.603

GnomAD4 genome AF: 0.550 AC: 83701 AN: 152060 Hom.: 24204 Cov.: 32 AF XY: 0.559 AC XY: 41541 AN XY: 74330

Gnomad4 AFR AF: 0.360

Gnomad4 AMR AF: 0.617

Gnomad4 ASJ AF: 0.662

Gnomad4 EAS AF: 0.710

Gnomad4 SAS AF: 0.663

Gnomad4 FIN AF: 0.660

Gnomad4 NFE AF: 0.607

Gnomad4 OTH AF: 0.557

Alfa AF: 0.602 Hom.: 32251

Bravo AF: 0.540

Asia WGS AF: 0.607 AC: 2113 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Jun 14, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

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Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Mitochondrial DNA depletion syndrome 1 Benign:1

Jul 10, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.1
DANN	Benign	0.43

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: rs470119; hg19: chr22-50966914;