Genetic Variant SAFB:p.Val603Leu (chr19-5657292-G-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001201338.2(SAFB):c.1807G>T(p.Val603Leu) 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. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V603A) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

SAFB
NM_001201338.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.62

Publications

0 publications found

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]

SAFB links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.07520148).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001201338.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SAFB	NM_001201338.2	MANE Select	c.1807G>T	p.Val603Leu	missense	Exon 14 of 21	NP_001188267.1	Q15424-3
SAFB	NM_001201339.2		c.1807G>T	p.Val603Leu	missense	Exon 14 of 21	NP_001188268.1	Q15424-4
SAFB	NM_002967.4		c.1807G>T	p.Val603Leu	missense	Exon 14 of 21	NP_002958.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SAFB	ENST00000588852.2	TSL:1 MANE Select	c.1807G>T	p.Val603Leu	missense	Exon 14 of 21	ENSP00000467423.1	Q15424-3
SAFB	ENST00000592224.5	TSL:1	c.1807G>T	p.Val603Leu	missense	Exon 14 of 21	ENSP00000464840.1	Q15424-4
SAFB	ENST00000292123.9	TSL:1	c.1807G>T	p.Val603Leu	missense	Exon 14 of 21	ENSP00000292123.4	Q15424-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000398

AC:

AN:

251406

AF XY:

0.00000736

show subpopulations

Gnomad AFR exome

AF:

0.0000616

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.28

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.60

CADD

Benign

(source)

DANN

Benign

0.28

DEOGEN2

Benign

0.13

Eigen

Benign

-0.50

Eigen_PC

Benign

-0.27

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.77

M_CAP

Benign

0.012

MetaRNN

Benign

0.075

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.99

PhyloP100

1.6

PrimateAI

Uncertain

0.65

PROVEAN

Benign

0.81

REVEL

Benign

0.069

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.039

Vest4

0.25

MutPred

0.19

Loss of helix (P = 0.0558)

MVP

0.31

MPC

0.86

ClinPred

0.087

GERP RS

5.5

PromoterAI

-0.035

Neutral

(source)

Varity_R

0.031

gMVP

0.050

Mutation Taster

=86/14

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over