Menu
GeneBe

19-5654392-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001201338.2(SAFB):c.1691T>C(p.Val564Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

SAFB
NM_001201338.2 missense

Scores

3
9
7

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.50
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 Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SAFBNM_001201338.2 linkuse as main transcriptc.1691T>C p.Val564Ala missense_variant 13/21 ENST00000588852.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SAFBENST00000588852.2 linkuse as main transcriptc.1691T>C p.Val564Ala missense_variant 13/211 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 GeneticsFeb 02, 2024The c.1691T>C (p.V564A) alteration is located in exon 13 (coding exon 13) of the SAFB gene. This alteration results from a T to C substitution at nucleotide position 1691, causing the valine (V) at amino acid position 564 to be replaced by an alanine (A). 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
Pathogenic
0.99
BayesDel_addAF
Uncertain
0.096
D
BayesDel_noAF
Benign
-0.10
CADD
Pathogenic
29
DANN
Uncertain
0.99
DEOGEN2
Benign
0.30
T;.;.;.
Eigen
Uncertain
0.62
Eigen_PC
Uncertain
0.54
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.94
D;D;D;D
M_CAP
Benign
0.044
D
MetaRNN
Uncertain
0.55
D;D;D;D
MetaSVM
Benign
-1.0
T
MutationAssessor
Uncertain
2.5
M;M;.;M
MutationTaster
Benign
1.0
D;D;D;D;D;D
PrimateAI
Pathogenic
0.82
D
PROVEAN
Uncertain
-3.0
D;.;D;.
REVEL
Uncertain
0.33
Sift
Benign
0.034
D;.;D;.
Sift4G
Benign
0.073
T;T;T;T
Polyphen
1.0
D;.;.;.
Vest4
0.61
MutPred
0.23
Gain of sheet (P = 0.0073);Gain of sheet (P = 0.0073);.;Gain of sheet (P = 0.0073);
MVP
0.49
MPC
2.1
ClinPred
0.97
D
GERP RS
5.3
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.12
gMVP
0.24

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.040
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: chr19-5654403; API