19-5654153-A-G
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Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_001201338.2(SAFB):āc.1619A>Gā(p.Asp540Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000479 in 1,461,884 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 (ā ).
Frequency
Genomes: not found (cov: 32)
Exomes š: 0.0000048 ( 0 hom. )
Consequence
SAFB
NM_001201338.2 missense
NM_001201338.2 missense
Scores
10
9
Clinical Significance
Conservation
PhyloP100: 4.51
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 -6 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.19441617).
BS2
High AC in GnomAdExome4 at 7 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SAFB | NM_001201338.2 | c.1619A>G | p.Asp540Gly | missense_variant | 12/21 | ENST00000588852.2 | NP_001188267.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SAFB | ENST00000588852.2 | c.1619A>G | p.Asp540Gly | missense_variant | 12/21 | 1 | NM_001201338.2 | ENSP00000467423.1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome AF: 0.00000479 AC: 7AN: 1461884Hom.: 0 Cov.: 32 AF XY: 0.00000550 AC XY: 4AN XY: 727244
GnomAD4 exome
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AC:
7
AN:
1461884
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Cov.:
32
AF XY:
AC XY:
4
AN XY:
727244
Gnomad4 AFR exome
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GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
Bravo
AF:
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 | May 15, 2023 | The c.1619A>G (p.D540G) alteration is located in exon 12 (coding exon 12) of the SAFB gene. This alteration results from a A to G substitution at nucleotide position 1619, causing the aspartic acid (D) at amino acid position 540 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Uncertain
T;.;.;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D;D
M_CAP
Benign
D
MetaRNN
Benign
T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;M;.;M
MutationTaster
Benign
D;D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;.;D;.
REVEL
Benign
Sift
Uncertain
D;.;D;.
Sift4G
Benign
T;T;T;T
Polyphen
B;.;.;.
Vest4
MutPred
Loss of solvent accessibility (P = 0.0477);Loss of solvent accessibility (P = 0.0477);.;Loss of solvent accessibility (P = 0.0477);
MVP
MPC
1.6
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_DG_spliceai
Position offset: -1
Find out detailed SpliceAI scores and Pangolin per-transcript scores at