NM_018169.4:c.436G>T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_018169.4(RESF1):​c.436G>T​(p.Val146Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Consequence

RESF1
NM_018169.4 missense

Scores

19

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.29
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]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.018462181).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RESF1NM_018169.4 linkc.436G>T p.Val146Leu 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.436G>T p.Val146Leu missense_variant Exon 4 of 6 1 NM_018169.4 ENSP00000310338.4 Q9HCM1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.0000120
AC:
3
AN:
250928
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135684
show subpopulations
Gnomad AFR exome
AF:
0.000186
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
Cov.:
44
GnomAD4 genome
Cov.:
32
ExAC
AF:
0.000585
AC:
71

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.098
BayesDel_addAF
Benign
-0.42
T
BayesDel_noAF
Benign
-0.61
CADD
Benign
0.0080
DANN
Benign
0.64
DEOGEN2
Benign
0.0084
T;.
Eigen
Benign
-1.8
Eigen_PC
Benign
-2.0
FATHMM_MKL
Benign
0.091
N
LIST_S2
Benign
0.48
T;T
M_CAP
Benign
0.0025
T
MetaRNN
Benign
0.018
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.34
N;.
PrimateAI
Benign
0.17
T
PROVEAN
Benign
-0.60
N;N
REVEL
Benign
0.045
Sift
Benign
0.33
T;T
Sift4G
Benign
0.44
T;T
Polyphen
0.0020
B;.
Vest4
0.032
MutPred
0.21
Gain of disorder (P = 0.1606);Gain of disorder (P = 0.1606);
MVP
0.048
MPC
0.0090
ClinPred
0.027
T
GERP RS
-11
Varity_R
0.024
gMVP
0.067

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: rs138851326; hg19: chr12-32134325; API