NM_001201338.2:c.11C>G

Variant names:

• chr19-5623216-C-G
• rs1246757204
• NM_001201338.2:c.11C>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001201338.2(SAFB):​c.11C>G​(p.Thr4Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000693 in 1,442,484 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: SAFB NM_001201338.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.32

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]

SAFB2 (HGNC:21605): (scaffold attachment factor B2) The protein encoded by this gene, along with its paralog (scaffold attachment factor B1), is a repressor of estrogen receptor alpha. The encoded protein binds scaffold/matrix attachment region (S/MAR) DNA and is involved in cell cycle regulation, apoptosis, differentiation, the stress response, and regulation of immune genes. [provided by RefSeq, May 2016]

ACMG classification

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=0.081389755).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SAFB	NM_001201338.2	c.11C>G	p.Thr4Ser	missense_variant	Exon 1 of 21	ENST00000588852.2	NP_001188267.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SAFB	ENST00000588852.2	c.11C>G	p.Thr4Ser	missense_variant	Exon 1 of 21	1	NM_001201338.2	ENSP00000467423.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000466 AC: 1 AN: 214658 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 116840

Gnomad AFR exome AF: 0.0000792

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.93e-7 AC: 1 AN: 1442484 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 716298

Gnomad4 AFR exome AF: 0.0000304

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.096
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	19
DANN	Benign	0.86
DEOGEN2	Benign	0.10	T;.;.;.
Eigen	Benign	-0.36
Eigen_PC	Benign	-0.20
FATHMM_MKL	Benign	0.67	D
LIST_S2	Benign	0.67	T;T;T;T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.081	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L;L;L;L
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-0.20	N;.;N;.
REVEL	Benign	0.11
Sift	Benign	0.57	T;.;T;.
Sift4G	Benign	0.84	T;T;T;T
Polyphen		0.012	B;.;.;.
Vest4		0.18
MutPred		0.051		Gain of phosphorylation at T4 (P = 0.0452);Gain of phosphorylation at T4 (P = 0.0452);Gain of phosphorylation at T4 (P = 0.0452);Gain of phosphorylation at T4 (P = 0.0452);
MVP		0.46
MPC		1.6
ClinPred		0.12	T
GERP RS		2.8
RBP_binding_hub_radar		0.97
RBP_regulation_power_radar		2.1
Varity_R		0.082
gMVP		0.089

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

LitVar

Other links and lift over

dbSNP: rs1246757204; hg19: chr19-5623227;