11-77667369-C-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_016578.4(RSF1):​c.3874G>A​(p.Glu1292Lys) variant causes a missense change. The variant allele was found at a frequency of 0.0000242 in 1,613,710 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000026 ( 0 hom. )

Consequence

RSF1
NM_016578.4 missense

Scores

1
10
8

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.80
Variant links:
Genes affected
RSF1 (HGNC:18118): (remodeling and spacing factor 1) This gene encodes a nuclear protein that interacts with hepatitis B virus X protein (HBX) and facilitates transcription of hepatitis B virus genes by the HBX transcription activator, suggesting a role for this interaction in the virus life cycle. This protein also interacts with SNF2H protein to form the RSF chromatin-remodeling complex, where the SNF2H subunit functions as the nucleosome-dependent ATPase, and this protein as the histone chaperone. [provided by RefSeq, Sep 2011]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.22479719).
BS2
High AC in GnomAdExome4 at 38 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RSF1NM_016578.4 linkc.3874G>A p.Glu1292Lys missense_variant Exon 16 of 16 ENST00000308488.11 NP_057662.3 Q96T23-1Q05DG0
RSF1XM_005274051.3 linkc.3865G>A p.Glu1289Lys missense_variant Exon 16 of 16 XP_005274108.1
RSF1XM_017017923.2 linkc.3751G>A p.Glu1251Lys missense_variant Exon 16 of 16 XP_016873412.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
RSF1ENST00000308488.11 linkc.3874G>A p.Glu1292Lys missense_variant Exon 16 of 16 1 NM_016578.4 ENSP00000311513.6 Q96T23-1
RSF1ENST00000480887.5 linkc.3118G>A p.Glu1040Lys missense_variant Exon 11 of 11 1 ENSP00000434509.1 Q96T23-3

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152110
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000199
AC:
5
AN:
251248
Hom.:
0
AF XY:
0.0000147
AC XY:
2
AN XY:
135786
show subpopulations
Gnomad AFR exome
AF:
0.00
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:
0.0000440
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000260
AC:
38
AN:
1461600
Hom.:
0
Cov.:
32
AF XY:
0.0000275
AC XY:
20
AN XY:
727122
show subpopulations
Gnomad4 AFR exome
AF:
0.0000598
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000297
Gnomad4 OTH exome
AF:
0.0000497
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152110
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74292
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000378
ExAC
AF:
0.0000165
AC:
2
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Mar 29, 2022
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.3874G>A (p.E1292K) alteration is located in exon 16 (coding exon 16) of the RSF1 gene. This alteration results from a G to A substitution at nucleotide position 3874, causing the glutamic acid (E) at amino acid position 1292 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.14
BayesDel_addAF
Benign
0.0015
T
BayesDel_noAF
Benign
-0.11
CADD
Pathogenic
27
DANN
Uncertain
1.0
DEOGEN2
Benign
0.055
T;.
Eigen
Uncertain
0.46
Eigen_PC
Uncertain
0.51
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.89
D;D
M_CAP
Benign
0.081
D
MetaRNN
Benign
0.22
T;T
MetaSVM
Uncertain
0.26
D
MutationAssessor
Uncertain
2.2
M;.
PrimateAI
Uncertain
0.51
T
PROVEAN
Benign
-0.86
N;N
REVEL
Uncertain
0.30
Sift
Uncertain
0.0050
D;D
Sift4G
Uncertain
0.019
D;D
Polyphen
0.94
P;.
Vest4
0.26
MutPred
0.14
Gain of ubiquitination at E1292 (P = 0.009);.;
MVP
0.56
MPC
0.38
ClinPred
0.46
T
GERP RS
4.9
RBP_binding_hub_radar
0.92
RBP_regulation_power_radar
2.0
Varity_R
0.17
gMVP
0.19

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: rs777265824; hg19: chr11-77378414; API