10-104124119-T-C

Position:

• chr10-104124119-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001002759.2(SFR1):​c.541T>C​(p.Ser181Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: SFR1 NM_001002759.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.87

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SFR1	NM_001002759.2	c.541T>C	p.Ser181Pro	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	c.541T>C	p.Ser181Pro	missense_variant	3/4	2	NM_001002759.2	ENSP00000358742	A1
SFR1	ENST00000369729.7	c.502T>C	p.Ser168Pro	missense_variant	3/4	1		ENSP00000358744	P4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

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

Dec 15, 2023

The c.541T>C (p.S181P) alteration is located in exon 3 (coding exon 3) of the SFR1 gene. This alteration results from a T to C substitution at nucleotide position 541, causing the serine (S) at amino acid position 181 to be replaced by a proline (P). 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	Pathogenic	0.94
BayesDel_addAF	Uncertain	0.034	T
BayesDel_noAF	Benign	-0.19
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.28	.;T
Eigen	Uncertain	0.56
Eigen_PC	Uncertain	0.53
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.81	T;T
M_CAP	Benign	0.029	D
MetaRNN	Uncertain	0.49	T;T
MetaSVM	Benign	-0.60	T
MutationAssessor	Uncertain	2.6	.;M
MutationTaster	Benign	0.98	D;D;D
PrimateAI	Uncertain	0.61	T
PROVEAN	Uncertain	-3.0	D;D
REVEL	Benign	0.21
Sift	Benign	0.059	T;D
Sift4G	Benign	0.068	T;T
Polyphen		1.0	.;D
Vest4		0.55
MutPred		0.49		.;Loss of phosphorylation at S181 (P = 0.0342);
MVP		0.38
MPC		0.13
ClinPred		0.98	D
GERP RS		4.6
Varity_R		0.59
gMVP		0.61

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: chr10-105883877;