12-31981273-C-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

1
17

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.71
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

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
RESF1NM_018169.4 linkc.318C>A p.His106Gln missense_variant Exon 4 of 6 ENST00000312561.9 NP_060639.4 Q9HCM1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
RESF1ENST00000312561.9 linkc.318C>A p.His106Gln missense_variant Exon 4 of 6 1 NM_018169.4 ENSP00000310338.4 Q9HCM1

Frequencies

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

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