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GeneBe

19-5661775-G-A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_001201338.2(SAFB):c.2120G>A(p.Arg707Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000957 in 1,567,644 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 31)
Exomes 𝑓: 0.0000078 ( 0 hom. )

Consequence

SAFB
NM_001201338.2 missense

Scores

2
10
7

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.76
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 -4 ACMG points.

BS2
High AC in GnomAdExome4 at 11 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SAFBNM_001201338.2 linkuse as main transcriptc.2120G>A p.Arg707Gln missense_variant 15/21 ENST00000588852.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SAFBENST00000588852.2 linkuse as main transcriptc.2120G>A p.Arg707Gln missense_variant 15/211 NM_001201338.2 P5Q15424-3

Frequencies

GnomAD3 genomes
AF:
0.0000263
AC:
4
AN:
152216
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.0000241
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:
0.0000441
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000587
AC:
1
AN:
170358
Hom.:
0
AF XY:
0.0000107
AC XY:
1
AN XY:
93190
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:
0.0000406
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000777
AC:
11
AN:
1415428
Hom.:
0
Cov.:
32
AF XY:
0.00000714
AC XY:
5
AN XY:
700078
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:
0.0000123
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000917
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000263
AC:
4
AN:
152216
Hom.:
0
Cov.:
31
AF XY:
0.0000134
AC XY:
1
AN XY:
74368
show subpopulations
Gnomad4 AFR
AF:
0.0000241
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:
0.0000441
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000151
ExAC
AF:
0.0000172
AC:
2

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 GeneticsOct 17, 2023The c.2120G>A (p.R707Q) alteration is located in exon 15 (coding exon 15) of the SAFB gene. This alteration results from a G to A substitution at nucleotide position 2120, causing the arginine (R) at amino acid position 707 to be replaced by a glutamine (Q). 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
0.27
BayesDel_addAF
Benign
-0.043
T
BayesDel_noAF
Benign
-0.30
CADD
Pathogenic
27
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.72
D;.;.;.;T
Eigen
Uncertain
0.58
Eigen_PC
Uncertain
0.56
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Pathogenic
0.98
D;D;D;D;D
M_CAP
Benign
0.048
D
MetaRNN
Uncertain
0.47
T;T;T;T;T
MetaSVM
Benign
-0.86
T
MutationAssessor
Uncertain
2.3
M;.;.;M;.
MutationTaster
Benign
1.0
D;D;D;D;D;D
PrimateAI
Uncertain
0.72
T
PROVEAN
Uncertain
-3.2
D;.;D;.;.
REVEL
Benign
0.20
Sift
Uncertain
0.0010
D;.;D;.;.
Sift4G
Uncertain
0.0030
D;D;D;D;T
Polyphen
0.99
D;.;.;.;.
Vest4
0.67
MutPred
0.21
Loss of MoRF binding (P = 0.0349);.;.;Loss of MoRF binding (P = 0.0349);.;
MVP
0.55
MPC
0.90
ClinPred
0.95
D
GERP RS
4.1
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.2
Varity_R
0.27
gMVP
0.69

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.

Other links and lift over

dbSNP: rs758546855; hg19: chr19-5661786; API