11-77675185-T-C

Position:

• chr11-77675185-T-C

Variant summary

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

The NM_016578.4(RSF1):​c.3413A>G​(p.Asp1138Gly) 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: 4.05

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]

RSF1 (HGNC:):

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=0.34316504).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RSF1	NM_016578.4	c.3413A>G	p.Asp1138Gly	missense_variant	14/16	ENST00000308488.11	NP_057662.3
RSF1	XM_005274051.3	c.3404A>G	p.Asp1135Gly	missense_variant	14/16		XP_005274108.1
RSF1	XM_017017923.2	c.3290A>G	p.Asp1097Gly	missense_variant	14/16		XP_016873412.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RSF1	ENST00000308488.11	c.3413A>G	p.Asp1138Gly	missense_variant	14/16	1	NM_016578.4	ENSP00000311513.6
RSF1	ENST00000480887.5	c.2657A>G	p.Asp886Gly	missense_variant	9/11	1		ENSP00000434509.1
RSF1	ENST00000531026.5	c.740A>G	p.Asp247Gly	missense_variant	8/8	1		ENSP00000433603.1
RSF1	ENST00000529470.1	n.342A>G		non_coding_transcript_exon_variant	2/2	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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 26, 2024

The c.3413A>G (p.D1138G) alteration is located in exon 14 (coding exon 14) of the RSF1 gene. This alteration results from a A to G substitution at nucleotide position 3413, causing the aspartic acid (D) at amino acid position 1138 to be replaced by a glycine (G). 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	0.48
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.040
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.034	T;.;.
Eigen	Uncertain	0.36
Eigen_PC	Uncertain	0.42
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.82	T;T;T
M_CAP	Benign	0.080	D
MetaRNN	Benign	0.34	T;T;T
MetaSVM	Uncertain	0.42	D
MutationAssessor	Benign	1.2	L;.;.
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	-2.1	N;N;N
REVEL	Uncertain	0.50
Sift	Uncertain	0.0040	D;D;T
Sift4G	Benign	0.40	T;T;.
Polyphen		0.85	P;.;.
Vest4		0.57
MutPred		0.15		Gain of MoRF binding (P = 0.073);.;.;
MVP		0.60
MPC		2.1
ClinPred		0.80	D
GERP RS		5.0
Varity_R		0.20
gMVP		0.21

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: chr11-77386230;