1-100274929-T-C

Variant names:

• chr1-100274929-T-C
• rs116538743
• NM_003729.4:c.579T>C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_003729.4(RTCA):​c.579T>C​(p.Tyr193Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0128 in 1,611,728 control chromosomes in the GnomAD database, including 176 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0094 (14 hom., cov: 33)
  • Exomes 𝑓: 0.013 (162 hom.)
• Consequence: RTCA NM_003729.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.155

Genes affected

RTCA (HGNC:17981): (RNA 3'-terminal phosphate cyclase) This gene encodes a member of the RNA 3'-phosphate cyclase family. The encoded protein plays a role in RNA metabolism by catalyzing the ATP-dependent conversion of the 3'-phosphate of RNA substrates to a 2',3'-cyclic phosphodiester. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Feb 2012]

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BP6: Variant 1-100274929-T-C is Benign according to our data. Variant chr1-100274929-T-C is described in ClinVar as [Benign]. Clinvar id is 776339.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.155 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4_exome allele frequency = 0.0131 (19147/1459376) while in subpopulation NFE AF= 0.0158 (17576/1110260). AF 95% confidence interval is 0.0156. There are 162 homozygotes in gnomad4_exome. There are 9115 alleles in male gnomad4_exome subpopulation. Median coverage is 30. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 14 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RTCA	NM_003729.4	c.579T>C	p.Tyr193Tyr	synonymous_variant	Exon 6 of 11	ENST00000370128.9	NP_003720.1
RTCA	NM_001130841.2	c.618T>C	p.Tyr206Tyr	synonymous_variant	Exon 7 of 12		NP_001124313.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RTCA	ENST00000370128.9	c.579T>C	p.Tyr193Tyr	synonymous_variant	Exon 6 of 11	1	NM_003729.4	ENSP00000359146.4
RTCA	ENST00000260563.4	c.618T>C	p.Tyr206Tyr	synonymous_variant	Exon 7 of 12	1		ENSP00000260563.4
RTCA	ENST00000498617.5	n.*86T>C		downstream_gene_variant		5

Frequencies

GnomAD3 genomes AF: 0.00938 AC: 1428 AN: 152234 Hom.: 14 Cov.: 33

Gnomad AFR AF: 0.00282

Gnomad AMI AF: 0.0252

Gnomad AMR AF: 0.00844

Gnomad ASJ AF: 0.00979

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00452

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0156

Gnomad OTH AF: 0.00764

GnomAD3 exomes AF: 0.00804 AC: 2020 AN: 251092 Hom.: 14 AF XY: 0.00796 AC XY: 1080 AN XY: 135712

Gnomad AFR exome AF: 0.00332

Gnomad AMR exome AF: 0.00551

Gnomad ASJ exome AF: 0.00695

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000393

Gnomad FIN exome AF: 0.00434

Gnomad NFE exome AF: 0.0136

Gnomad OTH exome AF: 0.00849

GnomAD4 exome AF: 0.0131 AC: 19147 AN: 1459376 Hom.: 162 Cov.: 30 AF XY: 0.0126 AC XY: 9115 AN XY: 725928

Gnomad4 AFR exome AF: 0.00239

Gnomad4 AMR exome AF: 0.00611

Gnomad4 ASJ exome AF: 0.00763

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000500

Gnomad4 FIN exome AF: 0.00499

Gnomad4 NFE exome AF: 0.0158

Gnomad4 OTH exome AF: 0.0117

GnomAD4 genome AF: 0.00937 AC: 1427 AN: 152352 Hom.: 14 Cov.: 33 AF XY: 0.00848 AC XY: 632 AN XY: 74502

Gnomad4 AFR AF: 0.00281

Gnomad4 AMR AF: 0.00837

Gnomad4 ASJ AF: 0.00979

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00452

Gnomad4 NFE AF: 0.0156

Gnomad4 OTH AF: 0.00756

Alfa AF: 0.0123 Hom.: 18

Bravo AF: 0.00948

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 20, 2018

Labcorp Genetics (formerly Invitae), Labcorp

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	-0.50
CADD	Benign	5.6
DANN	Benign	0.48

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: rs116538743; hg19: chr1-100740485;