11-77667287-T-C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2BP4_ModerateBS2

The NM_016578.4(RSF1):​c.3956A>G​(p.Asn1319Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,872 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

RSF1
NM_016578.4 missense

Scores

1
1
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.19

Publications

0 publications found
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 was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.13028082).
BS2
High AC in GnomAdExome4 at 5 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RSF1NM_016578.4 linkc.3956A>G p.Asn1319Ser missense_variant Exon 16 of 16 ENST00000308488.11 NP_057662.3 Q96T23-1Q05DG0
RSF1XM_005274051.3 linkc.3947A>G p.Asn1316Ser missense_variant Exon 16 of 16 XP_005274108.1
RSF1XM_017017923.2 linkc.3833A>G p.Asn1278Ser 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.3956A>G p.Asn1319Ser missense_variant Exon 16 of 16 1 NM_016578.4 ENSP00000311513.6 Q96T23-1
RSF1ENST00000480887.5 linkc.3200A>G p.Asn1067Ser missense_variant Exon 11 of 11 1 ENSP00000434509.1 Q96T23-3

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000342
AC:
5
AN:
1461872
Hom.:
0
Cov.:
31
AF XY:
0.00000413
AC XY:
3
AN XY:
727240
show subpopulations
African (AFR)
AF:
0.0000299
AC:
1
AN:
33480
American (AMR)
AF:
0.00
AC:
0
AN:
44724
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26136
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39698
South Asian (SAS)
AF:
0.00
AC:
0
AN:
86256
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53406
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5768
European-Non Finnish (NFE)
AF:
0.00000360
AC:
4
AN:
1112008
Other (OTH)
AF:
0.00
AC:
0
AN:
60396
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.525
Heterozygous variant carriers
0
1
2
2
3
4
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
Cov.:
32
Alfa
AF:
0.00
Hom.:
0
Bravo
AF:
0.00000378

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Apr 18, 2025
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing

The c.3956A>G (p.N1319S) alteration is located in exon 16 (coding exon 16) of the RSF1 gene. This alteration results from a A to G substitution at nucleotide position 3956, causing the asparagine (N) at amino acid position 1319 to be replaced by a serine (S). 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
0.055
BayesDel_addAF
Benign
-0.16
T
BayesDel_noAF
Benign
-0.47
CADD
Benign
14
DANN
Uncertain
0.99
DEOGEN2
Benign
0.0049
T;.
Eigen
Benign
-0.34
Eigen_PC
Benign
-0.15
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Benign
0.77
T;T
M_CAP
Benign
0.020
T
MetaRNN
Benign
0.13
T;T
MetaSVM
Benign
-0.68
T
MutationAssessor
Benign
0.0
N;.
PhyloP100
3.2
PrimateAI
Benign
0.29
T
PROVEAN
Benign
-0.59
N;N
REVEL
Benign
0.26
Sift
Benign
0.038
D;D
Sift4G
Benign
0.32
T;T
Polyphen
0.0010
B;.
Vest4
0.048
MutPred
0.13
Loss of solvent accessibility (P = 0.0193);.;
MVP
0.41
MPC
0.13
ClinPred
0.18
T
GERP RS
4.9
RBP_binding_hub_radar
0.92
RBP_regulation_power_radar
2.7
Varity_R
0.049
gMVP
0.029
Mutation Taster
=96/4
polymorphism

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

Other links and lift over

dbSNP: rs1377669463; hg19: chr11-77378332; API