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GeneBe

19-5641851-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001201338.2(SAFB):c.451G>C(p.Asp151His) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Consequence

SAFB
NM_001201338.2 missense

Scores

1
1
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.13
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 Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.13892376).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SAFBNM_001201338.2 linkuse as main transcriptc.451G>C p.Asp151His missense_variant 4/21 ENST00000588852.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SAFBENST00000588852.2 linkuse as main transcriptc.451G>C p.Asp151His missense_variant 4/211 NM_001201338.2 P5Q15424-3

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
31

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 16, 2023The c.451G>C (p.D151H) alteration is located in exon 4 (coding exon 4) of the SAFB gene. This alteration results from a G to C substitution at nucleotide position 451, causing the aspartic acid (D) at amino acid position 151 to be replaced by a histidine (H). 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
0.12
BayesDel_addAF
Benign
-0.22
T
BayesDel_noAF
Benign
-0.55
CADD
Benign
21
DANN
Uncertain
0.99
DEOGEN2
Benign
0.16
T;.;.
Eigen
Benign
0.12
Eigen_PC
Benign
0.21
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Benign
0.63
T;T;T
M_CAP
Benign
0.024
T
MetaRNN
Benign
0.14
T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.0
L;L;L
MutationTaster
Benign
1.0
D;D;D;D;D;D
PrimateAI
Benign
0.45
T
PROVEAN
Benign
0.060
N;.;.
REVEL
Benign
0.10
Sift
Benign
0.064
T;.;.
Sift4G
Benign
0.18
T;T;T
Polyphen
0.47
P;.;.
Vest4
0.19
MutPred
0.25
Gain of catalytic residue at D150 (P = 0.0728);Gain of catalytic residue at D150 (P = 0.0728);Gain of catalytic residue at D150 (P = 0.0728);
MVP
0.34
MPC
0.43
ClinPred
0.48
T
GERP RS
4.5
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.046
gMVP
0.056

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-5641862; API