rs116538743

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 publications found

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

Our verdict: Benign. The variant received -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 VariationId 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. GnomAdExome4 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 GnomAdExome4. There are 9115 alleles in the male GnomAdExome4 subpopulation. Median coverage is 30. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 14 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003729.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RTCA	NM_003729.4	MANE Select	c.579T>C	p.Tyr193Tyr	synonymous	Exon 6 of 11	NP_003720.1	O00442-1
	RTCA	NM_001130841.2		c.618T>C	p.Tyr206Tyr	synonymous	Exon 7 of 12	NP_001124313.1	O00442-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RTCA	ENST00000370128.9	TSL:1 MANE Select	c.579T>C	p.Tyr193Tyr	synonymous	Exon 6 of 11	ENSP00000359146.4	O00442-1
	RTCA	ENST00000260563.4	TSL:1	c.618T>C	p.Tyr206Tyr	synonymous	Exon 7 of 12	ENSP00000260563.4	O00442-2
	RTCA	ENST00000881959.1		c.579T>C	p.Tyr193Tyr	synonymous	Exon 6 of 12	ENSP00000552018.1

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

GnomAD2 exomes AF: 0.00804 AC: 2020 AN: 251092 AF XY: 0.00796

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 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

African (AFR) AF: 0.00239 AC: 80 AN: 33460

American (AMR) AF: 0.00611 AC: 273 AN: 44662

Ashkenazi Jewish (ASJ) AF: 0.00763 AC: 199 AN: 26068

East Asian (EAS) AF: 0.00 AC: 0 AN: 39640

South Asian (SAS) AF: 0.000500 AC: 43 AN: 85976

European-Finnish (FIN) AF: 0.00499 AC: 266 AN: 53296

Middle Eastern (MID) AF: 0.000869 AC: 5 AN: 5756

European-Non Finnish (NFE) AF: 0.0158 AC: 17576 AN: 1110260

Other (OTH) AF: 0.0117 AC: 705 AN: 60258

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

African (AFR) AF: 0.00281 AC: 117 AN: 41590

American (AMR) AF: 0.00837 AC: 128 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00979 AC: 34 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00452 AC: 48 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0156 AC: 1061 AN: 68026

Other (OTH) AF: 0.00756 AC: 16 AN: 2116

Alfa AF: 0.0121 Hom.: 38

Bravo AF: 0.00948

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	5.6
DANN	Benign	0.48
PhyloP100		0.15
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs116538743; hg19: chr1-100740485;