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GeneBe

19-5654437-C-G

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_001201338.2(SAFB):c.1736C>G(p.Thr579Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000618 in 1,455,330 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: 32)
Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

SAFB
NM_001201338.2 missense

Scores

1
6
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.65
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]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.3465258).
BS2
High AC in GnomAdExome4 at 9 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SAFBNM_001201338.2 linkuse as main transcriptc.1736C>G p.Thr579Arg missense_variant 13/21 ENST00000588852.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SAFBENST00000588852.2 linkuse as main transcriptc.1736C>G p.Thr579Arg missense_variant 13/211 NM_001201338.2 P5Q15424-3

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251476
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135916
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:
0.00000879
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000618
AC:
9
AN:
1455330
Hom.:
0
Cov.:
29
AF XY:
0.00000414
AC XY:
3
AN XY:
724492
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:
0.00000814
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Alfa
AF:
0.0000492
Hom.:
0

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 GeneticsDec 27, 2023The c.1736C>G (p.T579R) alteration is located in exon 13 (coding exon 13) of the SAFB gene. This alteration results from a C to G substitution at nucleotide position 1736, causing the threonine (T) at amino acid position 579 to be replaced by an arginine (R). 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
Benign
-0.014
T
BayesDel_noAF
Benign
-0.26
CADD
Uncertain
25
DANN
Benign
0.93
DEOGEN2
Benign
0.25
T;.;.;.
Eigen
Uncertain
0.19
Eigen_PC
Benign
0.064
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.93
D;D;D;D
M_CAP
Benign
0.022
T
MetaRNN
Benign
0.35
T;T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Uncertain
2.4
M;M;.;M
MutationTaster
Benign
1.0
D;D;D;D;D;D
PrimateAI
Uncertain
0.69
T
PROVEAN
Uncertain
-3.6
D;.;D;.
REVEL
Benign
0.16
Sift
Benign
0.12
T;.;T;.
Sift4G
Benign
0.17
T;T;T;T
Polyphen
0.99
D;.;.;.
Vest4
0.53
MutPred
0.23
Loss of phosphorylation at T579 (P = 0.0457);Loss of phosphorylation at T579 (P = 0.0457);.;Loss of phosphorylation at T579 (P = 0.0457);
MVP
0.37
MPC
2.0
ClinPred
0.97
D
GERP RS
3.2
Varity_R
0.16
gMVP
0.21

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.030
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: rs867493353; hg19: chr19-5654448; API