rs1023559794

Variant names:

• chr19-18431826-C-G
• rs1023559794
• NM_032627.5:c.529C>G

Variant summary

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

The NM_032627.5(SSBP4):​c.529C>G​(p.Leu177Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000353 in 1,415,886 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000035 (0 hom.)
• Consequence: SSBP4 NM_032627.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.76
• Publications: 0 publications found

Genes affected

SSBP4 (HGNC:15676): (single stranded DNA binding protein 4) Predicted to enable single-stranded DNA binding activity. Predicted to be involved in positive regulation of transcription by RNA polymerase II. Predicted to be integral component of membrane. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

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=0.222875).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032627.5. 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
	SSBP4	NM_032627.5	MANE Select	c.529C>G	p.Leu177Val	missense	Exon 8 of 18	NP_116016.1	Q9BWG4-1
	SSBP4	NM_001009998.4		c.463C>G	p.Leu155Val	missense	Exon 7 of 17	NP_001009998.1	Q9BWG4-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SSBP4	ENST00000270061.12	TSL:1 MANE Select	c.529C>G	p.Leu177Val	missense	Exon 8 of 18	ENSP00000270061.5	Q9BWG4-1
	SSBP4	ENST00000915352.1		c.463C>G	p.Leu155Val	missense	Exon 7 of 17	ENSP00000585411.1
	SSBP4	ENST00000867041.1		c.469C>G	p.Leu157Val	missense	Exon 7 of 17	ENSP00000537100.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000168 AC: 3 AN: 178716 AF XY: 0.0000103

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000408

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000353 AC: 5 AN: 1415886 Hom.: 0 Cov.: 33 AF XY: 0.00000286 AC XY: 2 AN XY: 699686

African (AFR) AF: 0.00 AC: 0 AN: 32384

American (AMR) AF: 0.00 AC: 0 AN: 38998

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25328

East Asian (EAS) AF: 0.00 AC: 0 AN: 37082

South Asian (SAS) AF: 0.00 AC: 0 AN: 81216

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49156

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5700

European-Non Finnish (NFE) AF: 0.00000460 AC: 5 AN: 1087558

Other (OTH) AF: 0.00 AC: 0 AN: 58464

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

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	0.11
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	19
DANN	Uncertain	0.98
DEOGEN2	Benign	0.028	T
Eigen	Benign	-0.41
Eigen_PC	Benign	-0.39
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-0.89	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		3.8
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.23
Sift	Uncertain	0.0050	D
Sift4G	Benign	0.20	T
Polyphen		0.0070	B
Vest4		0.41
MutPred		0.43		Loss of glycosylation at P178 (P = 0.1261)
MVP		0.068
MPC		0.23
ClinPred		0.24	T
GERP RS		1.8
PromoterAI		-0.10	Neutral
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.8
Varity_R		0.10
gMVP		0.13
Mutation Taster		=87/13	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs1023559794; hg19: chr19-18542636;