12-31981273-C-A

Variant names:

• chr12-31981273-C-A
• rs2388981
• NM_018169.4:c.318C>A

Variant summary

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

The NM_018169.4(RESF1):​c.318C>A​(p.His106Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.186 in 1,613,698 control chromosomes in the GnomAD database, including 29,360 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency:
  • Genomes: 𝑓 0.16 (2161 hom., cov: 32)
  • Exomes 𝑓: 0.19 (27199 hom.)
• Consequence: RESF1 NM_018169.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.71
• Publications: 20 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0048665404).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.214 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RESF1	NM_018169.4	MANE Select	c.318C>A	p.His106Gln	missense	Exon 4 of 6	NP_060639.4	Q9HCM1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RESF1	ENST00000312561.9	TSL:1 MANE Select	c.318C>A	p.His106Gln	missense	Exon 4 of 6	ENSP00000310338.4	Q9HCM1
	RESF1	ENST00000913392.1		c.318C>A	p.His106Gln	missense	Exon 2 of 4	ENSP00000583451.1
	RESF1	ENST00000913394.1		c.318C>A	p.His106Gln	missense	Exon 5 of 7	ENSP00000583453.1

Frequencies

GnomAD3 genomes AF: 0.156 AC: 23744 AN: 152070 Hom.: 2162 Cov.: 32

Gnomad AFR AF: 0.0783

Gnomad AMI AF: 0.385

Gnomad AMR AF: 0.143

Gnomad ASJ AF: 0.231

Gnomad EAS AF: 0.0909

Gnomad SAS AF: 0.227

Gnomad FIN AF: 0.182

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.195

Gnomad OTH AF: 0.166

GnomAD2 exomes AF: 0.171 AC: 42985 AN: 251080 AF XY: 0.180

Gnomad AFR exome AF: 0.0752

Gnomad AMR exome AF: 0.102

Gnomad ASJ exome AF: 0.220

Gnomad EAS exome AF: 0.0799

Gnomad FIN exome AF: 0.185

Gnomad NFE exome AF: 0.195

Gnomad OTH exome AF: 0.196

GnomAD4 exome AF: 0.189 AC: 276714 AN: 1461510 Hom.: 27199 Cov.: 36 AF XY: 0.192 AC XY: 139504 AN XY: 727068

African (AFR) AF: 0.0757 AC: 2535 AN: 33476

American (AMR) AF: 0.108 AC: 4837 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.222 AC: 5807 AN: 26130

East Asian (EAS) AF: 0.120 AC: 4766 AN: 39690

South Asian (SAS) AF: 0.235 AC: 20303 AN: 86242

European-Finnish (FIN) AF: 0.179 AC: 9540 AN: 53376

Middle Eastern (MID) AF: 0.250 AC: 1442 AN: 5768

European-Non Finnish (NFE) AF: 0.194 AC: 216114 AN: 1111730

Other (OTH) AF: 0.188 AC: 11370 AN: 60378

GnomAD4 genome AF: 0.156 AC: 23739 AN: 152188 Hom.: 2161 Cov.: 32 AF XY: 0.156 AC XY: 11587 AN XY: 74402

African (AFR) AF: 0.0785 AC: 3260 AN: 41516

American (AMR) AF: 0.142 AC: 2174 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.231 AC: 803 AN: 3472

East Asian (EAS) AF: 0.0910 AC: 471 AN: 5178

South Asian (SAS) AF: 0.225 AC: 1085 AN: 4822

European-Finnish (FIN) AF: 0.182 AC: 1927 AN: 10592

Middle Eastern (MID) AF: 0.259 AC: 76 AN: 294

European-Non Finnish (NFE) AF: 0.195 AC: 13246 AN: 68004

Other (OTH) AF: 0.164 AC: 347 AN: 2116

Alfa AF: 0.175 Hom.: 6546

Bravo AF: 0.148

TwinsUK AF: 0.200 AC: 743

ALSPAC AF: 0.190 AC: 734

ESP6500AA AF: 0.0794 AC: 350

ESP6500EA AF: 0.201 AC: 1726

ExAC AF: 0.175 AC: 21219

Asia WGS AF: 0.137 AC: 477 AN: 3478

EpiCase AF: 0.194

EpiControl AF: 0.198

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.77	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	0.0060
DANN	Benign	0.48
DEOGEN2	Benign	0.054	T
Eigen	Benign	-2.1
Eigen_PC	Benign	-2.2
FATHMM_MKL	Benign	0.050	N
LIST_S2	Benign	0.49	T
MetaRNN	Benign	0.0049	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.55	N
PhyloP100		-2.7
PrimateAI	Benign	0.24	T
PROVEAN	Uncertain	-3.3	D
REVEL	Benign	0.025
Sift	Benign	0.20	T
Sift4G	Benign	0.24	T
Polyphen		0.0020	B
Vest4		0.060
MutPred		0.66		Loss of catalytic residue at L108 (P = 0.082)
MPC		0.010
ClinPred		0.018	T
GERP RS		-11
Varity_R		0.069
gMVP		0.26
Mutation Taster		=98/2	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: rs2388981; hg19: chr12-32134207; COSMIC: COSV57022364; COSMIC: COSV57022364;