chr12-31981273-C-A

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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. 13/20 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 Likely benign in UniProt.

• 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

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 -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RESF1	NM_018169.4	c.318C>A	p.His106Gln	missense_variant	Exon 4 of 6	ENST00000312561.9	NP_060639.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RESF1	ENST00000312561.9	c.318C>A	p.His106Gln	missense_variant	Exon 4 of 6	1	NM_018169.4	ENSP00000310338.4

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

GnomAD3 exomes AF: 0.171 AC: 42985 AN: 251080 Hom.: 4029 AF XY: 0.180 AC XY: 24432 AN XY: 135694

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 SAS exome AF: 0.235

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

Gnomad4 AFR exome AF: 0.0757

Gnomad4 AMR exome AF: 0.108

Gnomad4 ASJ exome AF: 0.222

Gnomad4 EAS exome AF: 0.120

Gnomad4 SAS exome AF: 0.235

Gnomad4 FIN exome AF: 0.179

Gnomad4 NFE exome AF: 0.194

Gnomad4 OTH exome AF: 0.188

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

Gnomad4 AFR AF: 0.0785

Gnomad4 AMR AF: 0.142

Gnomad4 ASJ AF: 0.231

Gnomad4 EAS AF: 0.0910

Gnomad4 SAS AF: 0.225

Gnomad4 FIN AF: 0.182

Gnomad4 NFE AF: 0.195

Gnomad4 OTH AF: 0.164

Alfa AF: 0.165 Hom.: 1940

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 v4.3

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;T
MetaRNN	Benign	0.0049	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.55	N;.
PrimateAI	Benign	0.24	T
PROVEAN	Uncertain	-3.3	D;D
REVEL	Benign	0.025
Sift	Benign	0.20	T;T
Sift4G	Benign	0.24	T;T
Polyphen		0.0020	B;.
Vest4		0.060
MutPred		0.66		Loss of catalytic residue at L108 (P = 0.082);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

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: rs2388981; hg19: chr12-32134207; COSMIC: COSV57022364; COSMIC: COSV57022364;