rs201351158

Variant names:

• chr20-63694385-G-A
• rs201351158
• NM_001283009.2:c.3006G>A

Your query was ambiguous. Multiple possible variants found:

• chr20-63694385-G-A
• chr20-63694385-G-C
• chr20-63694385-G-T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6_Very_Strong BP7

The NM_001283009.2(RTEL1):​c.3006G>A​(p.Pro1002Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000946 in 1,575,202 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. P1002P) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.00010 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000094 (0 hom.)
• Consequence: RTEL1 NM_001283009.2 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -1.51
• Publications: 0 publications found

Genes affected

RTEL1 (HGNC:15888): (regulator of telomere elongation helicase 1) This gene encodes a DNA helicase which functions in the stability, protection and elongation of telomeres and interacts with proteins in the shelterin complex known to protect telomeres during DNA replication. Mutations in this gene have been associated with dyskeratosis congenita and Hoyerall-Hreidarsson syndrome. Read-through transcription of this gene into the neighboring downstream gene, which encodes tumor necrosis factor receptor superfamily, member 6b, generates a non-coding transcript. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Sep 2013]

RTEL1-TNFRSF6B (HGNC:44095): (RTEL1-TNFRSF6B readthrough (NMD candidate)) This locus represents naturally occurring read-through transcription between the neighboring RTEL1 (regulator of telomere elongation helicase 1) and TNFRSF6B (tumor necrosis factor receptor superfamily, member 6b, decoy) genes on chromosome 20. The read-through transcript is a candidate for nonsense-mediated mRNA decay (NMD), and is unlikely to produce a protein product. [provided by RefSeq, Feb 2011]

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 20-63694385-G-A is Benign according to our data. Variant chr20-63694385-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 540962.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.51 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001283009.2. 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
	RTEL1	NM_001283009.2	MANE Select	c.3006G>A	p.Pro1002Pro	synonymous	Exon 31 of 35	NP_001269938.1	Q9NZ71-6
	RTEL1	NM_032957.5		c.3078G>A	p.Pro1026Pro	synonymous	Exon 31 of 35	NP_116575.3	Q9NZ71-7
	RTEL1	NM_016434.4		c.3006G>A	p.Pro1002Pro	synonymous	Exon 31 of 35	NP_057518.1	Q9NZ71-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RTEL1	ENST00000360203.11	TSL:5 MANE Select	c.3006G>A	p.Pro1002Pro	synonymous	Exon 31 of 35	ENSP00000353332.5	Q9NZ71-6
	RTEL1	ENST00000508582.7	TSL:2	c.3078G>A	p.Pro1026Pro	synonymous	Exon 31 of 35	ENSP00000424307.2	Q9NZ71-7
	RTEL1	ENST00000370018.7	TSL:1	c.3006G>A	p.Pro1002Pro	synonymous	Exon 31 of 35	ENSP00000359035.3	Q9NZ71-1

Frequencies

GnomAD3 genomes AF: 0.000100 AC: 15 AN: 149476 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000977

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000266

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000204

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000892

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000121 AC: 30 AN: 247034 AF XY: 0.000171

Gnomad AFR exome AF: 0.0000624

Gnomad AMR exome AF: 0.000203

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000109

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000127

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000940 AC: 134 AN: 1425604 Hom.: 0 Cov.: 33 AF XY: 0.000100 AC XY: 71 AN XY: 708600

African (AFR) AF: 0.00 AC: 0 AN: 32562

American (AMR) AF: 0.000138 AC: 6 AN: 43576

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24932

East Asian (EAS) AF: 0.0000269 AC: 1 AN: 37206

South Asian (SAS) AF: 0.000198 AC: 17 AN: 85942

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49168

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5584

European-Non Finnish (NFE) AF: 0.0000974 AC: 106 AN: 1088520

Other (OTH) AF: 0.0000688 AC: 4 AN: 58114

GnomAD4 genome AF: 0.000100 AC: 15 AN: 149598 Hom.: 0 Cov.: 31 AF XY: 0.0000547 AC XY: 4 AN XY: 73094

African (AFR) AF: 0.0000974 AC: 4 AN: 41058

American (AMR) AF: 0.000266 AC: 4 AN: 15052

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3426

East Asian (EAS) AF: 0.000204 AC: 1 AN: 4904

South Asian (SAS) AF: 0.00 AC: 0 AN: 4590

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10064

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

European-Non Finnish (NFE) AF: 0.0000892 AC: 6 AN: 67228

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.0000993 Hom.: 0

Bravo AF: 0.0000869

EpiCase AF: 0.000218

EpiControl AF: 0.000356

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Dyskeratosis congenita, autosomal recessive 5;C4225346:Pulmonary fibrosis and/or bone marrow failure, Telomere-related, 3 (1)
-	-	1	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.082
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.2
DANN	Benign	0.64
PhyloP100		-1.5
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs201351158; hg19: chr20-62325738;