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GeneBe

19-5651007-G-A

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP3BS2

The NM_001201338.2(SAFB):c.1228G>A(p.Val410Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000056 in 1,608,044 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

SAFB
NM_001201338.2 missense

Scores

5
8
6

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.88
Variant links:
Genes affected
SAFB (HGNC:10520): (scaffold attachment factor B) This gene encodes a DNA-binding protein which has high specificity for scaffold or matrix attachment region DNA elements (S/MAR DNA). This protein is thought to be involved in attaching the base of chromatin loops to the nuclear matrix but there is conflicting evidence as to whether this protein is a component of chromatin or a nuclear matrix protein. Scaffold attachment factors are a specific subset of nuclear matrix proteins (NMP) that specifically bind to S/MAR. The encoded protein is thought to serve as a molecular base to assemble a 'transcriptosome complex' in the vicinity of actively transcribed genes. It is involved in the regulation of heat shock protein 27 transcription, can act as an estrogen receptor co-repressor and is a candidate for breast tumorigenesis. This gene is arranged head-to-head with a similar gene whose product has the same functions. Multiple transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Jan 2011]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PP3
MetaRNN computational evidence supports a deleterious effect, 0.777
BS2
High AC in GnomAdExome4 at 7 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SAFBNM_001201338.2 linkuse as main transcriptc.1228G>A p.Val410Ile missense_variant 9/21 ENST00000588852.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SAFBENST00000588852.2 linkuse as main transcriptc.1228G>A p.Val410Ile missense_variant 9/211 NM_001201338.2 P5Q15424-3

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152230
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.00000481
AC:
7
AN:
1455814
Hom.:
0
Cov.:
28
AF XY:
0.00000138
AC XY:
1
AN XY:
724172
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:
0.00000631
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152230
Hom.:
0
Cov.:
32
AF XY:
0.0000269
AC XY:
2
AN XY:
74380
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000756

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 submitterclinical testingAmbry GeneticsMar 20, 2023The c.1228G>A (p.V410I) alteration is located in exon 9 (coding exon 9) of the SAFB gene. This alteration results from a G to A substitution at nucleotide position 1228, causing the valine (V) at amino acid position 410 to be replaced by an isoleucine (I). 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
0.50
BayesDel_addAF
Uncertain
0.073
D
BayesDel_noAF
Benign
-0.13
CADD
Pathogenic
28
DANN
Uncertain
1.0
DEOGEN2
Benign
0.16
T;.;.;.
Eigen
Uncertain
0.65
Eigen_PC
Pathogenic
0.70
FATHMM_MKL
Pathogenic
1.0
D
LIST_S2
Pathogenic
0.98
D;D;D;D
M_CAP
Uncertain
0.14
D
MetaRNN
Pathogenic
0.78
D;D;D;D
MetaSVM
Uncertain
0.092
D
MutationAssessor
Benign
0.0050
N;N;.;N
MutationTaster
Benign
1.0
D;D;D;D;D;D
PrimateAI
Uncertain
0.61
T
PROVEAN
Benign
-0.90
N;.;N;.
REVEL
Uncertain
0.47
Sift
Benign
0.11
T;.;T;.
Sift4G
Pathogenic
0.0
D;D;D;D
Polyphen
0.99
D;.;.;.
Vest4
0.68
MutPred
0.74
Loss of sheet (P = 0.0817);Loss of sheet (P = 0.0817);.;Loss of sheet (P = 0.0817);
MVP
0.72
MPC
1.7
ClinPred
0.87
D
GERP RS
5.1
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.11
gMVP
0.49

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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.

Other links and lift over

dbSNP: rs2053926733; hg19: chr19-5651018; API