Variant 12-31981394-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_018169.4(RESF1):c.439C>T(p.Pro147Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00294 in 1,613,988 control chromosomes in the GnomAD database, including 134 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.016 ( 64 hom., cov: 32)

Exomes 𝑓: 0.0016 ( 70 hom. )

Consequence

RESF1
NM_018169.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.647

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]

RESF1 links:

RESF1 (HGNC:):

RESF1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0027252436).

BP6

Variant 12-31981394-C-T is Benign according to our data. Variant chr12-31981394-C-T is described in ClinVar as [Benign]. Clinvar id is 786225.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0523 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RESF1	NM_018169.4 linkuse as main transcript	c.439C>T	p.Pro147Ser	missense_variant	4/6	ENST00000312561.9	NP_060639.4	Q9HCM1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RESF1	ENST00000312561.9 linkuse as main transcript	c.439C>T	p.Pro147Ser	missense_variant	4/6	1	NM_018169.4	ENSP00000310338.4		Q9HCM1

Frequencies

GnomAD3 genomes

AF:

0.0155

AC:

2358

AN:

152146

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0541

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00543

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000147

Gnomad OTH

AF:

0.0110

GnomAD3 exomes

AF:

0.00426

AC:

1070

AN:

251230

Hom.:

AF XY:

0.00314

AC XY:

426

AN XY:

135794

show subpopulations

Gnomad AFR exome

AF:

0.0591

Gnomad AMR exome

AF:

0.00249

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000653

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000114

Gnomad OTH exome

AF:

0.00147

GnomAD4 exome

AF:

0.00163

AC:

2377

AN:

1461724

Hom.:

Cov.:

AF XY:

0.00137

AC XY:

996

AN XY:

727164

show subpopulations

Gnomad4 AFR exome

AF:

0.0578

Gnomad4 AMR exome

AF:

0.00288

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000580

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000675

Gnomad4 OTH exome

AF:

0.00359

GnomAD4 genome

AF:

0.0156

AC:

2368

AN:

152264

Hom.:

Cov.:

AF XY:

0.0149

AC XY:

1111

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.0542

Gnomad4 AMR

AF:

0.00543

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000147

Gnomad4 OTH

AF:

0.0109

Alfa

AF:

0.00337

Hom.:

Bravo

AF:

0.0179

ESP6500AA

AF:

0.0508

AC:

224

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.00521

AC:

633

Asia WGS

AF:

0.00491

AC:

AN:

3478

EpiCase

AF:

0.000273

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 30, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.090

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.51

CADD

Benign

0.98

DANN

Benign

0.80

DEOGEN2

Benign

0.048

T;.

Eigen

Benign

-0.87

Eigen_PC

Benign

-0.91

FATHMM_MKL

Benign

0.078

LIST_S2

Benign

0.54

T;T

MetaRNN

Benign

0.0027

T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

1.1

L;.

PrimateAI

Benign

0.18

PROVEAN

Uncertain

-3.4

D;D

REVEL

Benign

0.061

Sift

Benign

0.13

T;T

Sift4G

Benign

0.18

T;T

Polyphen

0.093

B;.

Vest4

0.10

MVP

0.099

MPC

0.014

ClinPred

0.010

GERP RS

1.1

Varity_R

0.037

gMVP

0.16

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over