NM_014649.3:c.2665T>G

Variant names:

• chr19-5587741-A-C
• NM_014649.3:c.2665T>G

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.2665T>G​(p.Ser889Ala) 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. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S889W) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: SAFB2 NM_014649.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.66
• 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=0.11217308).

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.2665T>G	p.Ser889Ala	missense	Exon 20 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.2665T>G	p.Ser889Ala	missense	Exon 20 of 21	ENSP00000252542.3	Q14151-1
	SAFB2	ENST00000912090.1		c.2683T>G	p.Ser895Ala	missense	Exon 20 of 21	ENSP00000582149.1
	SAFB2	ENST00000850599.1		c.2665T>G	p.Ser889Ala	missense	Exon 20 of 21	ENSP00000520886.1	Q14151-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

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	0.067
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	15
DANN	Benign	0.95
DEOGEN2	Benign	0.10	T
Eigen	Benign	-0.62
Eigen_PC	Benign	-0.64
FATHMM_MKL	Benign	0.55	D
LIST_S2	Benign	0.64	T
M_CAP	Benign	0.0065	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	L
PhyloP100		1.7
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.048
Sift	Benign	0.094	T
Sift4G	Benign	0.29	T
Polyphen		0.0010	B
Vest4		0.27
MutPred		0.15		Loss of glycosylation at S889 (P = 0.0025)
MVP		0.17
MPC		0.057
ClinPred		0.086	T
GERP RS		1.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.3
Varity_R		0.042
gMVP		0.081
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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

hg19: chr19-5587752;