ENST00000334944.9:c.1801G>T

Variant names:

• chr11-64765505-C-A
• ENST00000334944.9:c.1801G>T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The ENST00000334944.9(SF1):​c.1801G>T​(p.Gly601Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,457,554 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/15 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G601S) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: SF1 ENST00000334944.9 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0320

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.31767923).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SF1	NM_004630.4	c.*313G>T		3_prime_UTR_variant	Exon 13 of 13	ENST00000377390.8	NP_004621.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SF1	ENST00000377390	c.*313G>T		3_prime_UTR_variant	Exon 13 of 13	1	NM_004630.4	ENSP00000366607.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1457554 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 725212

Gnomad4 AFR exome AF: 0.00

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: 9.01e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	0.0019	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	13
DANN	Benign	0.97
Eigen	Benign	-0.0041
Eigen_PC	Benign	-0.11
FATHMM_MKL	Benign	0.75	D
LIST_S2	Benign	0.72	T;T
M_CAP	Uncertain	0.11	D
MetaRNN	Benign	0.32	T;T
MetaSVM	Benign	-0.79	T
PROVEAN	Benign	-1.1	N;N
REVEL	Benign	0.14
Sift	Pathogenic	0.0	D;D
Sift4G	Benign	0.11	T;T
Polyphen		1.0	D;D
Vest4		0.35
MutPred		0.15		.;Loss of relative solvent accessibility (P = 0.0071);
MVP		0.61
ClinPred		0.38	T
GERP RS		-2.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: chr11-64532977;