Variant 22-30356764-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_005877.6(SF3A1):c.29C>T(p.Pro10Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000754 in 1,326,942 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000075 ( 0 hom. )

Consequence

SF3A1
NM_005877.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.29

Variant links:

Genes affected

SF3A1 (HGNC:10765): (splicing factor 3a subunit 1) This gene encodes a subunit of the splicing factor 3a protein complex. The splicing factor 3a heterotrimer is a component of the mature U2 small nuclear ribonucleoprotein particle (snRNP). U2 small nuclear ribonucleoproteins play a critical role in spliceosome assembly and pre-mRNA splicing. [provided by RefSeq, Aug 2014]

SF3A1 links:

CCDC157 (HGNC:33854): (coiled-coil domain containing 157)

CCDC157 links:

SF3A1 (HGNC:):

SF3A1 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.14393729).

BS2

High AC in GnomAdExome4 at 10 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SF3A1	NM_005877.6 linkuse as main transcript	c.29C>T	p.Pro10Leu	missense_variant	1/16	ENST00000215793.13	NP_005868.1	Q15459-1A0A024R1K8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SF3A1	ENST00000215793.13 linkuse as main transcript	c.29C>T	p.Pro10Leu	missense_variant	1/16	1	NM_005877.6	ENSP00000215793.7		Q15459-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000859

AC:

AN:

116400

Hom.:

AF XY:

0.00

AC XY:

AN XY:

65990

show subpopulations

Gnomad AFR exome

AF:

0.00

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:

0.0000203

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000754

AC:

AN:

1326942

Hom.:

Cov.:

AF XY:

0.00000764

AC XY:

AN XY:

654424

show subpopulations

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:

0.00000959

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

Oct 26, 2022

The c.29C>T (p.P10L) alteration is located in exon 1 (coding exon 1) of the SF3A1 gene. This alteration results from a C to T substitution at nucleotide position 29, causing the proline (P) at amino acid position 10 to be replaced by a leucine (L). 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

0.086

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.40

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.076

Eigen

Benign

-0.0055

Eigen_PC

Benign

0.16

FATHMM_MKL

Benign

0.74

LIST_S2

Uncertain

0.86

M_CAP

Benign

0.022

MetaRNN

Benign

0.14

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.8

PrimateAI

Uncertain

0.76

PROVEAN

Benign

-0.34

REVEL

Benign

0.079

Sift

Benign

0.11

Sift4G

Benign

0.072

Polyphen

0.0030

Vest4

0.27

MutPred

0.27

Gain of sheet (P = 0.0149);

MVP

0.30

MPC

0.86

ClinPred

0.67

GERP RS

4.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.8

Varity_R

0.19

gMVP

0.18

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

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