19-5590348-G-C

Variant names:

• chr19-5590348-G-C
• rs376677397
• NM_014649.3:c.2455C>G

Variant summary

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

The NM_014649.3(SAFB2):​c.2455C>G​(p.Arg819Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,458,886 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 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: SAFB2 NM_014649.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.15

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2619721).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SAFB2	NM_014649.3	c.2455C>G	p.Arg819Gly	missense_variant	Exon 18 of 21	ENST00000252542.9	NP_055464.1
SAFB2	XM_011528449.4	c.2455C>G	p.Arg819Gly	missense_variant	Exon 18 of 21		XP_011526751.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SAFB2	ENST00000252542.9	c.2455C>G	p.Arg819Gly	missense_variant	Exon 18 of 21	1	NM_014649.3	ENSP00000252542.3
SAFB2	ENST00000589925.1	n.323C>G		non_coding_transcript_exon_variant	Exon 4 of 5	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1458886 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 725568

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000225

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

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.37	T
Eigen	Benign	-0.32
Eigen_PC	Benign	-0.17
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.0056	T
MetaRNN	Benign	0.26	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.7	L
PrimateAI	Uncertain	0.62	T
PROVEAN	Uncertain	-3.9	D
REVEL	Benign	0.079
Sift	Benign	0.058	T
Sift4G	Uncertain	0.028	D
Polyphen		0.022	B
Vest4		0.55
MutPred		0.26		Loss of solvent accessibility (P = 0.0299);
MVP		0.13
MPC		0.039
ClinPred		0.90	D
GERP RS		3.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.19
gMVP		0.10

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs376677397; hg19: chr19-5590359;