chr11-64767073-A-G

Position:

• chr11-64767073-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_004630.4(SF1):​c.1409T>C​(p.Met470Thr) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SF1 NM_004630.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.71

Genes affected

SF1 (HGNC:12950): (splicing factor 1) This gene encodes a nuclear pre-mRNA splicing factor. The encoded protein specifically recognizes the intron branch point sequence at the 3' splice site, together with the large subunit of U2 auxiliary factor (U2AF), and is required for the early stages of spliceosome assembly. It also plays a role in nuclear pre-mRNA retention and transcriptional repression. The encoded protein contains an N-terminal U2AF ligand motif, a central hnRNP K homology motif and quaking 2 region which bind a key branch-site adenosine within the branch point sequence, a zinc knuckles domain, and a C-terminal proline-rich domain. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2016]

SF1 (HGNC:):

ACMG classification

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=0.19014132).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SF1	NM_004630.4	c.1409T>C	p.Met470Thr	missense_variant	12/13	ENST00000377390.8	NP_004621.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SF1	ENST00000377390.8	c.1409T>C	p.Met470Thr	missense_variant	12/13	1	NM_004630.4	ENSP00000366607.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 35

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

Sep 30, 2024

The c.1784T>C (p.M595T) alteration is located in exon 12 (coding exon 12) of the SF1 gene. This alteration results from a T to C substitution at nucleotide position 1784, causing the methionine (M) at amino acid position 595 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	Uncertain	0.49
BayesDel_addAF	Benign	-0.061	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	23
DANN	Benign	0.84
DEOGEN2	Benign	0.15	.;T;.;.;T;.
Eigen	Benign	-0.027
Eigen_PC	Benign	0.12
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.85	T;D;T;T;T;D
M_CAP	Benign	0.069	D
MetaRNN	Benign	0.19	T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	.;L;L;L;.;.
PrimateAI	Pathogenic	0.87	D
PROVEAN	Benign	-0.66	N;N;N;N;N;N
REVEL	Benign	0.10
Sift	Uncertain	0.021	D;.;D;T;D;T
Sift4G	Benign	0.39	T;T;T;T;T;T
Polyphen		0.14	B;B;B;B;.;.
Vest4		0.68
MutPred		0.22		.;Gain of phosphorylation at M470 (P = 0.0069);Gain of phosphorylation at M470 (P = 0.0069);Gain of phosphorylation at M470 (P = 0.0069);.;.;
MVP		0.37
MPC		0.25
ClinPred		0.55	D
GERP RS		4.7
Varity_R		0.70
gMVP		0.11

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: chr11-64534545;