11-77667300-G-T

Variant names:

• chr11-77667300-G-T
• NM_016578.4:c.3943C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_016578.4(RSF1):​c.3943C>A​(p.His1315Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 17/22 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)
• Consequence: RSF1 NM_016578.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.77
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.079163045).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RSF1	NM_016578.4	c.3943C>A	p.His1315Asn	missense_variant	Exon 16 of 16	ENST00000308488.11	NP_057662.3
RSF1	XM_005274051.3	c.3934C>A	p.His1312Asn	missense_variant	Exon 16 of 16		XP_005274108.1
RSF1	XM_017017923.2	c.3820C>A	p.His1274Asn	missense_variant	Exon 16 of 16		XP_016873412.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RSF1	ENST00000308488.11	c.3943C>A	p.His1315Asn	missense_variant	Exon 16 of 16	1	NM_016578.4	ENSP00000311513.6
RSF1	ENST00000480887.5	c.3187C>A	p.His1063Asn	missense_variant	Exon 11 of 11	1		ENSP00000434509.1

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 06, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.3943C>A (p.H1315N) alteration is located in exon 16 (coding exon 16) of the RSF1 gene. This alteration results from a C to A substitution at nucleotide position 3943, causing the histidine (H) at amino acid position 1315 to be replaced by an asparagine (N). 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	0.064
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	18
DANN	Benign	0.87
DEOGEN2	Benign	0.0027	T;.
Eigen	Benign	-0.40
Eigen_PC	Benign	-0.15
FATHMM_MKL	Benign	0.63	D
LIST_S2	Benign	0.61	T;T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.079	T;T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	-1.6	N;.
PhyloP100		1.8
PrimateAI	Benign	0.44	T
PROVEAN	Benign	0.50	N;N
REVEL	Benign	0.21
Sift	Benign	0.47	T;T
Sift4G	Benign	1.0	T;T
Polyphen		0.0	B;.
Vest4		0.15
MutPred		0.12		Gain of relative solvent accessibility (P = 0.0166);.;
MVP		0.53
MPC		0.19
ClinPred		0.067	T
GERP RS		3.2
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.0
Varity_R		0.039
gMVP		0.11
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

Other links and lift over

hg19: chr11-77378345;