11-77675069-C-T

Variant names:

• chr11-77675069-C-T
• NM_016578.4:c.3529G>A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_016578.4(RSF1):​c.3529G>A​(p.Glu1177Lys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: RSF1 NM_016578.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.72

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.284626).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RSF1	NM_016578.4	c.3529G>A	p.Glu1177Lys	missense_variant	Exon 14 of 16	ENST00000308488.11	NP_057662.3
RSF1	XM_005274051.3	c.3520G>A	p.Glu1174Lys	missense_variant	Exon 14 of 16		XP_005274108.1
RSF1	XM_017017923.2	c.3406G>A	p.Glu1136Lys	missense_variant	Exon 14 of 16		XP_016873412.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RSF1	ENST00000308488.11	c.3529G>A	p.Glu1177Lys	missense_variant	Exon 14 of 16	1	NM_016578.4	ENSP00000311513.6
RSF1	ENST00000480887.5	c.2773G>A	p.Glu925Lys	missense_variant	Exon 9 of 11	1		ENSP00000434509.1
RSF1	ENST00000531026.5	c.*26G>A		downstream_gene_variant		1		ENSP00000433603.1
RSF1	ENST00000529470.1	n.*10G>A		downstream_gene_variant		2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 28, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.3529G>A (p.E1177K) alteration is located in exon 14 (coding exon 14) of the RSF1 gene. This alteration results from a G to A substitution at nucleotide position 3529, causing the glutamic acid (E) at amino acid position 1177 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	Pathogenic	0.80
BayesDel_addAF	Uncertain	0.10	D
BayesDel_noAF	Benign	-0.090
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.016	T;.
Eigen	Uncertain	0.41
Eigen_PC	Uncertain	0.47
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.89	D;D
M_CAP	Benign	0.060	D
MetaRNN	Benign	0.28	T;T
MetaSVM	Uncertain	0.20	D
MutationAssessor	Benign	1.6	L;.
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	-1.6	N;N
REVEL	Uncertain	0.41
Sift	Uncertain	0.012	D;D
Sift4G	Benign	0.074	T;T
Polyphen		0.89	P;.
Vest4		0.37
MutPred		0.19		Gain of ubiquitination at E1177 (P = 0.0114);.;
MVP		0.42
MPC		0.58
ClinPred		0.86	D
GERP RS		5.0
Varity_R		0.21
gMVP		0.30

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-77386114; COSMIC: COSV105159218; COSMIC: COSV105159218;