Variant 11-77676892-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_016578.4(RSF1):c.3241G>A(p.Ala1081Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000131 in 1,614,186 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000098 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00013 ( 4 hom. )

Consequence

RSF1
NM_016578.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.28

Variant links:

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 links:

RSF1 (HGNC:):

RSF1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.014071703).

BS2

High AC in GnomAd4 at 15 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RSF1	NM_016578.4 linkuse as main transcript	c.3241G>A	p.Ala1081Thr	missense_variant	13/16	ENST00000308488.11	NP_057662.3	Q96T23-1Q05DG0
RSF1	XM_005274051.3 linkuse as main transcript	c.3232G>A	p.Ala1078Thr	missense_variant	13/16		XP_005274108.1
RSF1	XM_017017923.2 linkuse as main transcript	c.3118G>A	p.Ala1040Thr	missense_variant	13/16		XP_016873412.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
RSF1	ENST00000308488.11 linkuse as main transcript	c.3241G>A	p.Ala1081Thr	missense_variant	13/16	1	NM_016578.4	ENSP00000311513.6	Q96T23-1
RSF1	ENST00000480887.5 linkuse as main transcript	c.2485G>A	p.Ala829Thr	missense_variant	8/11	1		ENSP00000434509.1	Q96T23-3
RSF1	ENST00000531026.5 linkuse as main transcript	c.568G>A	p.Ala190Thr	missense_variant	7/8	1		ENSP00000433603.1	H0YDG9
RSF1	ENST00000529470.1 linkuse as main transcript	n.170G>A		non_coding_transcript_exon_variant	1/2	2

Frequencies

GnomAD3 genomes

AF:

0.0000986

AC:

AN:

152202

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00310

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000283

AC:

AN:

251296

Hom.:

AF XY:

0.000353

AC XY:

AN XY:

135806

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00232

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000134

AC:

196

AN:

1461866

Hom.:

Cov.:

AF XY:

0.000186

AC XY:

135

AN XY:

727232

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00212

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.000166

GnomAD4 genome

AF:

0.0000985

AC:

AN:

152320

Hom.:

Cov.:

AF XY:

0.000188

AC XY:

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00310

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000113

ExAC

AF:

0.000313

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 20, 2024

The c.3241G>A (p.A1081T) alteration is located in exon 13 (coding exon 13) of the RSF1 gene. This alteration results from a G to A substitution at nucleotide position 3241, causing the alanine (A) at amino acid position 1081 to be replaced by a threonine (T). 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

0.17

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.13

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.016

T;.;.

Eigen

Benign

0.13

Eigen_PC

Uncertain

0.28

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.86

D;D;D

M_CAP

Benign

0.045

MetaRNN

Benign

0.014

T;T;T

MetaSVM

Uncertain

-0.11

MutationAssessor

Benign

1.9

L;.;.

PrimateAI

Uncertain

0.56

PROVEAN

Benign

-0.71

N;N;N

REVEL

Benign

0.20

Sift

Uncertain

0.014

D;D;T

Sift4G

Benign

0.35

T;T;.

Polyphen

0.30

B;.;.

Vest4

0.36

MutPred

0.31

Gain of phosphorylation at A1081 (P = 0.0058);.;.;

MVP

0.52

MPC

1.7

ClinPred

0.21

GERP RS

4.8

Varity_R

0.12

gMVP

0.12

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over