Variant 10-104123060-C-T 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.109C>T(p.Pro37Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000697 in 1,435,582 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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)

Exomes 𝑓: 7.0e-7 ( 0 hom. )

Consequence

SFR1
NM_001002759.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.418

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:

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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=0.086073846).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SFR1	NM_001002759.2 linkuse as main transcript	c.109C>T	p.Pro37Ser	missense_variant	2/4	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.109C>T	p.Pro37Ser	missense_variant	2/4	2	NM_001002759.2	ENSP00000358742	A1	Q86XK3-1
SFR1	ENST00000369729.7 linkuse as main transcript	c.70C>T	p.Pro24Ser	missense_variant	2/4	1		ENSP00000358744	P4	Q86XK3-3
SFR1	ENST00000463224.5 linkuse as main transcript	n.193C>T		non_coding_transcript_exon_variant	2/2	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.97e-7

AC:

AN:

1435582

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

712998

show subpopulations

Gnomad4 AFR exome

AF:

0.0000314

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

Cov.:

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

Sep 26, 2023

The c.109C>T (p.P37S) alteration is located in exon 2 (coding exon 2) of the SFR1 gene. This alteration results from a C to T substitution at nucleotide position 109, causing the proline (P) at amino acid position 37 to be replaced by a serine (S). 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

0.080

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.52

CADD

Benign

8.0

DANN

Benign

0.59

DEOGEN2

Benign

0.025

.;T

Eigen

Benign

-0.74

Eigen_PC

Benign

-0.77

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.59

T;T

M_CAP

Benign

0.010

MetaRNN

Benign

0.086

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.5

.;L

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.32

PROVEAN

Benign

-2.3

N;N

REVEL

Benign

0.045

Sift

Benign

0.075

T;T

Sift4G

Benign

0.13

T;T

Polyphen

0.022

.;B

Vest4

0.13

MutPred

0.47

.;Gain of phosphorylation at P37 (P = 0.0109);

MVP

0.10

MPC

0.022

ClinPred

0.094

GERP RS

3.6

Varity_R

0.059

gMVP

0.14

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over