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GeneBe

19-5657304-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM1PM2BP4_Moderate

The NM_001201338.2(SAFB):c.1819A>G(p.Lys607Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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)

Consequence

SAFB
NM_001201338.2 missense

Scores

9
10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.07
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 2 ACMG points.

PM1
In a modified_residue N6-acetyllysine (size 0) in uniprot entity SAFB1_HUMAN
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.19632584).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SAFBNM_001201338.2 linkuse as main transcriptc.1819A>G p.Lys607Glu missense_variant 14/21 ENST00000588852.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SAFBENST00000588852.2 linkuse as main transcriptc.1819A>G p.Lys607Glu missense_variant 14/211 NM_001201338.2 P5Q15424-3

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
32

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 17, 2023The c.1819A>G (p.K607E) alteration is located in exon 14 (coding exon 14) of the SAFB gene. This alteration results from a A to G substitution at nucleotide position 1819, causing the lysine (K) at amino acid position 607 to be replaced by a glutamic acid (E). 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
0.35
BayesDel_addAF
Benign
-0.13
T
BayesDel_noAF
Benign
-0.42
CADD
Uncertain
24
DANN
Uncertain
0.99
DEOGEN2
Uncertain
0.68
D;.;.;.
Eigen
Benign
-0.014
Eigen_PC
Benign
0.060
FATHMM_MKL
Uncertain
0.97
D
LIST_S2
Benign
0.76
T;T;T;T
M_CAP
Benign
0.016
T
MetaRNN
Benign
0.20
T;T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Uncertain
2.5
M;M;.;M
MutationTaster
Benign
1.0
D;D;D;D;D;D
PrimateAI
Uncertain
0.51
T
PROVEAN
Uncertain
-2.6
D;.;D;.
REVEL
Benign
0.039
Sift
Uncertain
0.014
D;.;D;.
Sift4G
Uncertain
0.020
D;D;D;D
Polyphen
0.50
P;.;.;.
Vest4
0.24
MutPred
0.26
Loss of methylation at K607 (P = 0.0067);Loss of methylation at K607 (P = 0.0067);.;Loss of methylation at K607 (P = 0.0067);
MVP
0.43
MPC
1.1
ClinPred
0.94
D
GERP RS
4.5
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.26
gMVP
0.31

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: chr19-5657315; COSMIC: COSV52652977; COSMIC: COSV52652977; API