11-77676990-C-G

Position:

• 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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.20

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]

ACMG classification

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
RSF1	NM_016578.4	c.3143G>C	p.Arg1048Pro	missense_variant	13/16	ENST00000308488.11	NP_057662.3
RSF1	XM_005274051.3	c.3134G>C	p.Arg1045Pro	missense_variant	13/16		XP_005274108.1
RSF1	XM_017017923.2	c.3020G>C	p.Arg1007Pro	missense_variant	13/16		XP_016873412.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RSF1	ENST00000308488.11	c.3143G>C	p.Arg1048Pro	missense_variant	13/16	1	NM_016578.4	ENSP00000311513	P1
RSF1	ENST00000480887.5	c.2387G>C	p.Arg796Pro	missense_variant	8/11	1		ENSP00000434509
RSF1	ENST00000531026.5	c.470G>C	p.Arg157Pro	missense_variant	7/8	1		ENSP00000433603
RSF1	ENST00000529470.1	n.72G>C		non_coding_transcript_exon_variant	1/2	2

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

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 10, 2024

The 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;