Genetic Variant NM_007165.5:c.1036C>T (chr19-2248187-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_007165.5(SF3A2):c.1036C>T(p.Pro346Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000768 in 1,302,258 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 29)

Exomes 𝑓: 7.7e-7 ( 0 hom. )

Consequence

SF3A2
NM_007165.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.01

Publications

1 publications found

Variant links:

Genes affected

SF3A2 (HGNC:10766): (splicing factor 3a subunit 2) This gene encodes subunit 2 of the splicing factor 3a protein complex. The splicing factor 3a heterotrimer includes subunits 1, 2 and 3 and is necessary for the in vitro conversion of 15S U2 snRNP into an active 17S particle that performs pre-mRNA splicing. Subunit 2 interacts with subunit 1 through its amino-terminus while the single zinc finger domain of subunit 2 plays a role in its binding to the 15S U2 snRNP. Subunit 2 may also function independently of its RNA splicing function as a microtubule-binding protein. [provided by RefSeq, Jul 2008]

SF3A2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.056649923).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007165.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SF3A2	NM_007165.5	MANE Select	c.1036C>T	p.Pro346Ser	missense	Exon 9 of 9	NP_009096.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SF3A2	ENST00000221494.10	TSL:1 MANE Select	c.1036C>T	p.Pro346Ser	missense	Exon 9 of 9	ENSP00000221494.3	Q15428
SF3A2	ENST00000866932.1		c.1138C>T	p.Pro380Ser	missense	Exon 9 of 9	ENSP00000536991.1
SF3A2	ENST00000866930.1		c.1036C>T	p.Pro346Ser	missense	Exon 10 of 10	ENSP00000536989.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000802

AC:

AN:

124744

AF XY:

0.0000146

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000210

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

7.68e-7

AC:

AN:

1302258

Hom.:

Cov.:

AF XY:

0.00000155

AC XY:

AN XY:

644462

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

29252

American (AMR)

AF:

0.00

AC:

AN:

33446

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22074

East Asian (EAS)

AF:

0.00

AC:

AN:

35524

South Asian (SAS)

AF:

0.00

AC:

AN:

74332

European-Finnish (FIN)

AF:

0.00

AC:

AN:

41014

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3792

European-Non Finnish (NFE)

AF:

9.92e-7

AC:

AN:

1008558

Other (OTH)

AF:

0.00

AC:

AN:

54266

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.069

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.69

CADD

Benign

(source)

DANN

Benign

0.76

DEOGEN2

Benign

0.056

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.70

M_CAP

Benign

0.063

MetaRNN

Benign

0.057

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.90

PhyloP100

-1.0

PrimateAI

Pathogenic

0.85

PROVEAN

Benign

-0.050

REVEL

Benign

0.043

Sift

Benign

0.18

Sift4G

Benign

0.10

Polyphen

0.0010

Vest4

0.20

MutPred

0.19

Gain of glycosylation at P346 (P = 0.0062)

MVP

0.26

MPC

0.64

ClinPred

0.055

GERP RS

-1.6

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.1

Varity_R

0.029

gMVP

0.19

Mutation Taster

=100/0

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over