Variant 10-104123952-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001002759.2(SFR1):c.374G>A(p.Cys125Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000118 in 1,613,858 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

SFR1
NM_001002759.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.60

Variant links:

Genes affected

SFR1 (HGNC:29574): (SWI5 dependent homologous recombination repair protein 1) Enables nuclear receptor coactivator activity. Involved in cellular response to estrogen stimulus; double-strand break repair via homologous recombination; and positive regulation of transcription, DNA-templated. Located in nucleus. Part of Swi5-Sfr1 complex. [provided by Alliance of Genome Resources, Apr 2022]

SFR1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.100544214).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SFR1	NM_001002759.2 linkuse as main transcript	c.374G>A	p.Cys125Tyr	missense_variant	3/4	ENST00000369727.4	NP_001002759.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SFR1	ENST00000369727.4 linkuse as main transcript	c.374G>A	p.Cys125Tyr	missense_variant	3/4	2	NM_001002759.2	ENSP00000358742	A1	Q86XK3-1
SFR1	ENST00000369729.7 linkuse as main transcript	c.335G>A	p.Cys112Tyr	missense_variant	3/4	1		ENSP00000358744	P4	Q86XK3-3

Frequencies

GnomAD3 genomes

AF:

0.0000657

AC:

AN:

152220

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000279

AC:

AN:

250662

Hom.:

AF XY:

0.0000369

AC XY:

AN XY:

135676

show subpopulations

Gnomad AFR exome

AF:

0.000439

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000616

AC:

AN:

1461520

Hom.:

Cov.:

AF XY:

0.00000963

AC XY:

AN XY:

727062

show subpopulations

Gnomad4 AFR exome

AF:

0.000269

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000656

AC:

AN:

152338

Hom.:

Cov.:

AF XY:

0.0000940

AC XY:

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000164

Hom.:

Bravo

AF:

0.0000680

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000330

AC:

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

Jan 23, 2023

The c.374G>A (p.C125Y) alteration is located in exon 3 (coding exon 3) of the SFR1 gene. This alteration results from a G to A substitution at nucleotide position 374, causing the cysteine (C) at amino acid position 125 to be replaced by a tyrosine (Y). 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

0.096

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Benign

0.70

DEOGEN2

Benign

0.050

.;T

Eigen

Benign

-0.25

Eigen_PC

Benign

-0.40

FATHMM_MKL

Benign

0.17

LIST_S2

Benign

0.57

T;T

M_CAP

Benign

0.011

MetaRNN

Benign

0.10

T;T

MetaSVM

Benign

-0.96

MutationAssessor

Uncertain

2.2

.;M

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.43

PROVEAN

Uncertain

-4.3

D;D

REVEL

Benign

0.15

Sift

Benign

0.47

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.99

.;D

Vest4

0.24

MVP

0.20

MPC

0.020

ClinPred

0.59

GERP RS

1.6

Varity_R

0.18

gMVP

0.10

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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