rs6999

Variant names:

• chr20-56518845-A-G
• rs6999
• NM_016407.5:c.*580A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016407.5(RTF2):​c.*580A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.412 in 151,908 control chromosomes in the GnomAD database, including 13,434 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.41 (13430 hom., cov: 31)
  • Exomes 𝑓: 0.53 (4 hom.)
• Consequence: RTF2 NM_016407.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0160
• Publications: 14 publications found

Genes affected

RTF2 (HGNC:15890): (replication termination factor 2) Enables DNA binding activity. Involved in cellular response to hydroxyurea and regulation of DNA stability. Located in replication fork. [provided by Alliance of Genome Resources, Apr 2022]

GCNT7 (HGNC:16099): (glucosaminyl (N-acetyl) transferase family member 7) Predicted to enable acetylglucosaminyltransferase activity. Predicted to be involved in protein glycosylation. Predicted to be located in Golgi membrane. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

FAM209A (HGNC:16100): (family with sequence similarity 209 member A) Located in extracellular exosome and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.442 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016407.5. 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
	RTF2	NM_016407.5	MANE Select	c.*580A>G		3_prime_UTR	Exon 9 of 9	NP_057491.2	Q9BY42
	RTF2	NM_001283035.2		c.*580A>G		3_prime_UTR	Exon 10 of 10	NP_001269964.1	A0A0A0MQR2
	RTF2	NM_001283036.2		c.*580A>G		3_prime_UTR	Exon 9 of 9	NP_001269965.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RTF2	ENST00000357348.10	TSL:1 MANE Select	c.*580A>G		3_prime_UTR	Exon 9 of 9	ENSP00000349906.6	Q9BY42
	GCNT7	ENST00000243913.8	TSL:2	c.-929-4540T>C		intron	N/A	ENSP00000243913.4	Q6ZNI0
	RTF2	ENST00000477573.1	TSL:1	n.2151A>G		non_coding_transcript_exon	Exon 3 of 3

Frequencies

GnomAD3 genomes AF: 0.412 AC: 62503 AN: 151752 Hom.: 13426 Cov.: 31

Gnomad AFR AF: 0.431

Gnomad AMI AF: 0.385

Gnomad AMR AF: 0.363

Gnomad ASJ AF: 0.310

Gnomad EAS AF: 0.0567

Gnomad SAS AF: 0.322

Gnomad FIN AF: 0.444

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.447

Gnomad OTH AF: 0.384

GnomAD4 exome AF: 0.526 AC: 20 AN: 38 Hom.: 4 Cov.: 0 AF XY: 0.450 AC XY: 9 AN XY: 20

African (AFR) AF: 0.500 AC: 1 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.567 AC: 17 AN: 30

Other (OTH) AF: 0.500 AC: 2 AN: 4

GnomAD4 genome AF: 0.412 AC: 62536 AN: 151870 Hom.: 13430 Cov.: 31 AF XY: 0.406 AC XY: 30113 AN XY: 74194

African (AFR) AF: 0.431 AC: 17852 AN: 41412

American (AMR) AF: 0.362 AC: 5525 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.310 AC: 1075 AN: 3466

East Asian (EAS) AF: 0.0566 AC: 292 AN: 5160

South Asian (SAS) AF: 0.321 AC: 1547 AN: 4820

European-Finnish (FIN) AF: 0.444 AC: 4663 AN: 10514

Middle Eastern (MID) AF: 0.310 AC: 91 AN: 294

European-Non Finnish (NFE) AF: 0.447 AC: 30333 AN: 67928

Other (OTH) AF: 0.383 AC: 807 AN: 2108

Alfa AF: 0.428 Hom.: 12642

Bravo AF: 0.403

Asia WGS AF: 0.197 AC: 688 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.2
DANN	Benign	0.55
PhyloP100		0.016
Mutation Taster		=100/0	polymorphism (auto)

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: rs6999; hg19: chr20-55093901;