NM_014649.3:c.2827C>A

Variant names:

• chr19-5587278-G-T
• NM_014649.3:c.2827C>A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_014649.3(SAFB2):​c.2827C>A​(p.Pro943Thr) 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. 14/21 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)
• Consequence: SAFB2 NM_014649.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.62

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

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2686228).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SAFB2	NM_014649.3	c.2827C>A	p.Pro943Thr	missense_variant	Exon 21 of 21	ENST00000252542.9	NP_055464.1
SAFB2	XM_011528449.4	c.*123C>A		3_prime_UTR_variant	Exon 21 of 21		XP_011526751.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SAFB2	ENST00000252542.9	c.2827C>A	p.Pro943Thr	missense_variant	Exon 21 of 21	1	NM_014649.3	ENSP00000252542.3
SAFB2	ENST00000587802.5	n.415C>A		non_coding_transcript_exon_variant	Exon 4 of 4	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.087
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	20
DANN	Benign	0.97
DEOGEN2	Benign	0.073	T
Eigen	Benign	0.068
Eigen_PC	Benign	0.014
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.58	T
M_CAP	Benign	0.0089	T
MetaRNN	Benign	0.27	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.69	N
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-0.42	N
REVEL	Benign	0.086
Sift	Uncertain	0.026	D
Sift4G	Benign	0.21	T
Polyphen		1.0	D
Vest4		0.34
MutPred		0.20		Gain of phosphorylation at P943 (P = 0.0051);
MVP		0.22
MPC		0.15
ClinPred		0.64	D
GERP RS		2.6
Varity_R		0.088
gMVP		0.30

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-5587289;