rs3759297

chr12-31984918-C-Gchr12-31984918-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_018169.4(RESF1):c.3963C>G(p.Thr1321=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.191 in 1,611,740 control chromosomes in the GnomAD database, including 30,582 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 0.17 (2426 hom., cov: 32)
  • Exomes 𝑓: 0.19 (28156 hom.)
• Consequence: RESF1 NM_018169.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.333

Genes affected

RESF1 (HGNC:25559): (retroelement silencing factor 1) Predicted to enable histone binding activity and histone methyltransferase binding activity. Predicted to be involved in negative regulation of single stranded viral RNA replication via double stranded DNA intermediate and positive regulation of DNA methylation-dependent heterochromatin assembly. Predicted to act upstream of or within response to bacterium. Predicted to be located in nucleus. Predicted to colocalize with gamma-tubulin complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP7: Synonymous conserved (PhyloP=-0.333 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.216 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RESF1	NM_018169.4	c.3963C>G	p.Thr1321=	synonymous_variant	4/6	ENST00000312561.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RESF1	ENST00000312561.9	c.3963C>G	p.Thr1321=	synonymous_variant	4/6	1	NM_018169.4	P1
RESF1	ENST00000397578.7	n.139-2321C>G		intron_variant, non_coding_transcript_variant		3
RESF1	ENST00000535596.5	n.318-2321C>G		intron_variant, non_coding_transcript_variant		2
RESF1	ENST00000541981.5	n.218-7460C>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.170 AC: 25838 AN: 151918 Hom.: 2428 Cov.: 32

Gnomad AFR AF: 0.116

Gnomad AMI AF: 0.385

Gnomad AMR AF: 0.149

Gnomad ASJ AF: 0.232

Gnomad EAS AF: 0.0903

Gnomad SAS AF: 0.229

Gnomad FIN AF: 0.198

Gnomad MID AF: 0.260

Gnomad NFE AF: 0.199

Gnomad OTH AF: 0.174

GnomAD3 exomes AF: 0.176 AC: 43852 AN: 249044 Hom.: 4189 AF XY: 0.184 AC XY: 24725 AN XY: 134464

Gnomad AFR exome AF: 0.112

Gnomad AMR exome AF: 0.103

Gnomad ASJ exome AF: 0.220

Gnomad EAS exome AF: 0.0794

Gnomad SAS exome AF: 0.233

Gnomad FIN exome AF: 0.200

Gnomad NFE exome AF: 0.199

Gnomad OTH exome AF: 0.200

GnomAD4 exome AF: 0.193 AC: 282159 AN: 1459704 Hom.: 28156 Cov.: 38 AF XY: 0.196 AC XY: 141939 AN XY: 725926

Gnomad4 AFR exome AF: 0.116

Gnomad4 AMR exome AF: 0.110

Gnomad4 ASJ exome AF: 0.222

Gnomad4 EAS exome AF: 0.120

Gnomad4 SAS exome AF: 0.235

Gnomad4 FIN exome AF: 0.195

Gnomad4 NFE exome AF: 0.197

Gnomad4 OTH exome AF: 0.193

GnomAD4 genome AF: 0.170 AC: 25835 AN: 152036 Hom.: 2426 Cov.: 32 AF XY: 0.170 AC XY: 12629 AN XY: 74302

Gnomad4 AFR AF: 0.116

Gnomad4 AMR AF: 0.148

Gnomad4 ASJ AF: 0.232

Gnomad4 EAS AF: 0.0903

Gnomad4 SAS AF: 0.228

Gnomad4 FIN AF: 0.198

Gnomad4 NFE AF: 0.199

Gnomad4 OTH AF: 0.172

Alfa AF: 0.191 Hom.: 937

Bravo AF: 0.162

Asia WGS AF: 0.139 AC: 483 AN: 3476

EpiCase AF: 0.196

EpiControl AF: 0.200

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	0.27
Dann	Benign	0.42

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: rs3759297; hg19: chr12-32137852; COSMIC: COSV57022408; COSMIC: COSV57022408;