NM_014649.3:c.2578C>G

Variant names:

• chr19-5587928-G-C
• rs376399865
• NM_014649.3:c.2578C>G

Variant summary

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

The NM_014649.3(SAFB2):​c.2578C>G​(p.Arg860Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,460,370 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R860C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: SAFB2 NM_014649.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.74
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SAFB2	NM_014649.3	c.2578C>G	p.Arg860Gly	missense_variant	Exon 19 of 21	ENST00000252542.9	NP_055464.1
SAFB2	XM_011528449.4	c.2578C>G	p.Arg860Gly	missense_variant	Exon 19 of 21		XP_011526751.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SAFB2	ENST00000252542.9	c.2578C>G	p.Arg860Gly	missense_variant	Exon 19 of 21	1	NM_014649.3	ENSP00000252542.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1460370 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 726482

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 33468

American (AMR) AF: 0.00 AC: 0 AN: 44684

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26096

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86168

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52352

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5766

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111828

Other (OTH) AF: 0.00 AC: 0 AN: 60314

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.038550), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.079
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.27	T
Eigen	Benign	-0.13
Eigen_PC	Benign	-0.19
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.022	T
MetaRNN	Uncertain	0.57	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		5.7
PrimateAI	Uncertain	0.50	T
PROVEAN	Uncertain	-3.2	D
REVEL	Benign	0.19
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.057	T
Polyphen		0.81	P
Vest4		0.67
MutPred		0.27		Loss of MoRF binding (P = 0.0016);
MVP		0.18
MPC		0.18
ClinPred		0.93	D
GERP RS		3.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.14
gMVP		0.14
Mutation Taster		=95/5	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: rs376399865; hg19: chr19-5587939;