Variant 12-45925014-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_ModerateBS2

The NM_004719.3(SCAF11):c.3620T>C(p.Met1207Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,870 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

SCAF11
NM_004719.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.38

Variant links:

Genes affected

SCAF11 (HGNC:10784): (SR-related CTD associated factor 11) Enables RNA binding activity. Involved in spliceosomal complex assembly. Located in nuclear body and nucleolus. [provided by Alliance of Genome Resources, Apr 2022]

SCAF11 links:

SCAF11 (HGNC:):

SCAF11 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.10048172).

BS2

High AC in GnomAdExome4 at 5 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCAF11	NM_004719.3 linkuse as main transcript	c.3620T>C	p.Met1207Thr	missense_variant	12/15	ENST00000369367.8	NP_004710.2	Q99590-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SCAF11	ENST00000369367.8 linkuse as main transcript	c.3620T>C	p.Met1207Thr	missense_variant	12/15	1	NM_004719.3	ENSP00000358374.3	Q99590-1
SCAF11	ENST00000549162.5 linkuse as main transcript	c.3044T>C	p.Met1015Thr	missense_variant	6/9	1		ENSP00000448864.1	F8VXG7
SCAF11	ENST00000465950.5 linkuse as main transcript	c.2675T>C	p.Met892Thr	missense_variant	2/5	1		ENSP00000449812.1	Q99590-2
SCAF11	ENST00000547950.1 linkuse as main transcript	n.630T>C		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000161

AC:

AN:

249042

Hom.:

AF XY:

0.0000223

AC XY:

AN XY:

134806

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000116

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000342

AC:

AN:

1461870

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

727234

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.0000894

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

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

Aug 28, 2023

The c.3620T>C (p.M1207T) alteration is located in exon 12 (coding exon 11) of the SCAF11 gene. This alteration results from a T to C substitution at nucleotide position 3620, causing the methionine (M) at amino acid position 1207 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

Benign

0.22

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Benign

0.92

DEOGEN2

Benign

0.041

T;.;T

Eigen

Benign

-0.14

Eigen_PC

Benign

-0.016

FATHMM_MKL

Benign

0.74

LIST_S2

Benign

0.75

T;T;T

M_CAP

Benign

0.011

MetaRNN

Benign

0.10

T;T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

1.6

L;.;.

MutationTaster

Benign

0.80

D;D;D;D

PrimateAI

Uncertain

0.54

PROVEAN

Benign

-1.8

N;N;N

REVEL

Benign

0.098

Sift

Uncertain

0.0010

D;D;D

Sift4G

Benign

0.089

T;T;T

Polyphen

0.013

B;.;.

Vest4

0.33

MutPred

0.30

Gain of glycosylation at M1207 (P = 0.0158);.;.;

MVP

0.082

MPC

0.044

ClinPred

0.27

GERP RS

3.9

Varity_R

0.50

gMVP

0.15

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