11-77667119-C-T

Position:

• chr11-77667119-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM1 PM2 BP4_Moderate

The NM_016578.4(RSF1):​c.4124G>A​(p.Ser1375Asn) 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: 3.98

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.

• PM1: In a modified_residue Phosphoserine (size 0) in uniprot entity RSF1_HUMAN
• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.25696117).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RSF1	NM_016578.4	c.4124G>A	p.Ser1375Asn	missense_variant	16/16	ENST00000308488.11	NP_057662.3
RSF1	XM_005274051.3	c.4115G>A	p.Ser1372Asn	missense_variant	16/16		XP_005274108.1
RSF1	XM_017017923.2	c.4001G>A	p.Ser1334Asn	missense_variant	16/16		XP_016873412.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RSF1	ENST00000308488.11	c.4124G>A	p.Ser1375Asn	missense_variant	16/16	1	NM_016578.4	ENSP00000311513.6
RSF1	ENST00000480887.5	c.3368G>A	p.Ser1123Asn	missense_variant	11/11	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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 26, 2022

The c.4124G>A (p.S1375N) alteration is located in exon 16 (coding exon 16) of the RSF1 gene. This alteration results from a G to A substitution at nucleotide position 4124, causing the serine (S) at amino acid position 1375 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	Uncertain	0.54
BayesDel_addAF	Benign	0.011	T
BayesDel_noAF	Benign	-0.22
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.024	T;.
Eigen	Uncertain	0.60
Eigen_PC	Uncertain	0.61
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.79	T;T
M_CAP	Benign	0.042	D
MetaRNN	Benign	0.26	T;T
MetaSVM	Uncertain	0.51	D
MutationAssessor	Benign	0.90	L;.
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-1.5	N;N
REVEL	Uncertain	0.33
Sift	Pathogenic	0.0	D;D
Sift4G	Uncertain	0.026	D;D
Polyphen		1.0	D;.
Vest4		0.32
MutPred		0.091		Loss of phosphorylation at S1375 (P = 0.1014);.;
MVP		0.39
MPC		0.68
ClinPred		0.81	D
GERP RS		4.8
Varity_R		0.33
gMVP		0.28

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: chr11-77378164;