NM_014649.3:c.2797G>C

Variant names:

• chr19-5587308-C-G
• rs1379389992
• NM_014649.3:c.2797G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014649.3(SAFB2):​c.2797G>C​(p.Gly933Arg) 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. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SAFB2 NM_014649.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.332
• Publications: 0 publications found

Genes affected

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

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=0.1966843).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014649.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SAFB2	NM_014649.3	MANE Select	c.2797G>C	p.Gly933Arg	missense	Exon 21 of 21	NP_055464.1	Q14151-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SAFB2	ENST00000252542.9	TSL:1 MANE Select	c.2797G>C	p.Gly933Arg	missense	Exon 21 of 21	ENSP00000252542.3	Q14151-1
	SAFB2	ENST00000912090.1		c.2815G>C	p.Gly939Arg	missense	Exon 21 of 21	ENSP00000582149.1
	SAFB2	ENST00000850599.1		c.2797G>C	p.Gly933Arg	missense	Exon 21 of 21	ENSP00000520886.1	Q14151-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.14	T
Eigen	Benign	-0.060
Eigen_PC	Benign	-0.15
FATHMM_MKL	Benign	0.37	N
LIST_S2	Benign	0.77	T
M_CAP	Benign	0.058	D
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	L
PhyloP100		0.33
PrimateAI	Benign	0.47	T
PROVEAN	Uncertain	-2.7	D
REVEL	Benign	0.057
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0050	D
Polyphen		0.91	P
Vest4		0.38
MutPred		0.19		Gain of solvent accessibility (P = 0.019)
MVP		0.068
MPC		0.25
ClinPred		0.98	D
GERP RS		4.1
Varity_R		0.25
gMVP		0.11
Mutation Taster		=92/8	polymorphism

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

Other links and lift over

dbSNP: rs1379389992; hg19: chr19-5587319;