12-31984918-C-G

Variant names:

• chr12-31984918-C-G
• rs3759297
• NM_018169.4:c.3963C>G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_018169.4(RESF1):​c.3963C>G​(p.Thr1321Thr) 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
• Publications: 13 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018169.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RESF1	NM_018169.4	MANE Select	c.3963C>G	p.Thr1321Thr	synonymous	Exon 4 of 6	NP_060639.4

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RESF1	ENST00000312561.9	TSL:1 MANE Select	c.3963C>G	p.Thr1321Thr	synonymous	Exon 4 of 6	ENSP00000310338.4
	RESF1	ENST00000397578.7	TSL:3	n.139-2321C>G		intron	N/A
	RESF1	ENST00000535596.5	TSL:2	n.318-2321C>G		intron	N/A

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

GnomAD2 exomes AF: 0.176 AC: 43852 AN: 249044 AF XY: 0.184

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 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

African (AFR) AF: 0.116 AC: 3859 AN: 33384

American (AMR) AF: 0.110 AC: 4871 AN: 44336

Ashkenazi Jewish (ASJ) AF: 0.222 AC: 5796 AN: 26078

East Asian (EAS) AF: 0.120 AC: 4760 AN: 39664

South Asian (SAS) AF: 0.235 AC: 20101 AN: 85364

European-Finnish (FIN) AF: 0.195 AC: 10379 AN: 53342

Middle Eastern (MID) AF: 0.253 AC: 1459 AN: 5762

European-Non Finnish (NFE) AF: 0.197 AC: 219281 AN: 1111436

Other (OTH) AF: 0.193 AC: 11653 AN: 60338

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

African (AFR) AF: 0.116 AC: 4825 AN: 41500

American (AMR) AF: 0.148 AC: 2265 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.232 AC: 803 AN: 3466

East Asian (EAS) AF: 0.0903 AC: 467 AN: 5170

South Asian (SAS) AF: 0.228 AC: 1097 AN: 4820

European-Finnish (FIN) AF: 0.198 AC: 2090 AN: 10548

Middle Eastern (MID) AF: 0.259 AC: 75 AN: 290

European-Non Finnish (NFE) AF: 0.199 AC: 13500 AN: 67946

Other (OTH) AF: 0.172 AC: 363 AN: 2116

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.27
DANN	Benign	0.42
PhyloP100		-0.33
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: rs3759297; hg19: chr12-32137852; COSMIC: COSV57022408; COSMIC: COSV57022408;