chr11-77676990-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The ENST00000308488.11(RSF1):​c.3143G>C​(p.Arg1048Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

RSF1
ENST00000308488.11 missense

Scores

5
11
3

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.20
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
RSF1NM_016578.4 linkuse as main transcriptc.3143G>C p.Arg1048Pro missense_variant 13/16 ENST00000308488.11 NP_057662.3
RSF1XM_005274051.3 linkuse as main transcriptc.3134G>C p.Arg1045Pro missense_variant 13/16 XP_005274108.1
RSF1XM_017017923.2 linkuse as main transcriptc.3020G>C p.Arg1007Pro missense_variant 13/16 XP_016873412.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
RSF1ENST00000308488.11 linkuse as main transcriptc.3143G>C p.Arg1048Pro missense_variant 13/161 NM_016578.4 ENSP00000311513 P1Q96T23-1
RSF1ENST00000480887.5 linkuse as main transcriptc.2387G>C p.Arg796Pro missense_variant 8/111 ENSP00000434509 Q96T23-3
RSF1ENST00000531026.5 linkuse as main transcriptc.470G>C p.Arg157Pro missense_variant 7/81 ENSP00000433603
RSF1ENST00000529470.1 linkuse as main transcriptn.72G>C non_coding_transcript_exon_variant 1/22

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
34
GnomAD4 genome
Cov.:
32

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsMay 10, 2024The c.3143G>C (p.R1048P) alteration is located in exon 13 (coding exon 13) of the RSF1 gene. This alteration results from a G to C substitution at nucleotide position 3143, causing the arginine (R) at amino acid position 1048 to be replaced by a proline (P). 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
Pathogenic
0.92
BayesDel_addAF
Pathogenic
0.31
D
BayesDel_noAF
Pathogenic
0.21
CADD
Pathogenic
29
DANN
Uncertain
1.0
DEOGEN2
Benign
0.15
T;.;.
Eigen
Uncertain
0.68
Eigen_PC
Uncertain
0.65
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Benign
0.83
T;T;D
M_CAP
Uncertain
0.18
D
MetaRNN
Uncertain
0.63
D;D;D
MetaSVM
Uncertain
0.79
D
MutationAssessor
Uncertain
2.4
M;.;.
MutationTaster
Benign
1.0
D;D;D
PrimateAI
Uncertain
0.76
T
PROVEAN
Pathogenic
-5.0
D;D;D
REVEL
Uncertain
0.40
Sift
Uncertain
0.0020
D;D;D
Sift4G
Uncertain
0.034
D;D;.
Polyphen
1.0
D;.;.
Vest4
0.85
MutPred
0.25
Loss of catalytic residue at R1048 (P = 0.034);.;.;
MVP
0.89
MPC
2.1
ClinPred
0.98
D
GERP RS
4.7
Varity_R
0.66
gMVP
0.42

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.070
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-77388035; API