19-18419661-G-C

Variant names:

• chr19-18419661-G-C
• rs907641600
• NM_032627.5:c.13G>C

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.13G>C​(p.Gly5Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000458 in 1,092,310 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000046 (0 hom.)
• Consequence: SSBP4 NM_032627.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.45
• 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=0.235138).

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.13G>C	p.Gly5Arg	missense	Exon 1 of 18	NP_116016.1	Q9BWG4-1
	SSBP4	NM_001009998.4		c.13G>C	p.Gly5Arg	missense	Exon 1 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.13G>C	p.Gly5Arg	missense	Exon 1 of 18	ENSP00000270061.5	Q9BWG4-1
	SSBP4	ENST00000915352.1		c.13G>C	p.Gly5Arg	missense	Exon 1 of 17	ENSP00000585411.1
	SSBP4	ENST00000867041.1		c.13G>C	p.Gly5Arg	missense	Exon 1 of 17	ENSP00000537100.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000458 AC: 5 AN: 1092310 Hom.: 0 Cov.: 31 AF XY: 0.00000567 AC XY: 3 AN XY: 528862

African (AFR) AF: 0.0000469 AC: 1 AN: 21300

American (AMR) AF: 0.000126 AC: 1 AN: 7962

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13244

East Asian (EAS) AF: 0.00 AC: 0 AN: 21666

South Asian (SAS) AF: 0.00 AC: 0 AN: 38360

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 23368

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3932

European-Non Finnish (NFE) AF: 0.00000326 AC: 3 AN: 920812

Other (OTH) AF: 0.00 AC: 0 AN: 41666

GnomAD4 genome Cov.: 31

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	Pathogenic	0.79
BayesDel_addAF	Benign	-0.0077	T
BayesDel_noAF	Benign	-0.25
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.033	T
Eigen	Benign	0.16
Eigen_PC	Benign	0.18
FATHMM_MKL	Benign	0.52	D
LIST_S2	Benign	0.69	T
M_CAP	Pathogenic	0.65	D
MetaRNN	Benign	0.24	T
MetaSVM	Benign	-0.61	T
MutationAssessor	Benign	0.69	N
PhyloP100		2.5
PrimateAI	Pathogenic	0.92	D
PROVEAN	Benign	-0.74	N
REVEL	Benign	0.11
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0020	D
Polyphen		0.83	P
Vest4		0.18
MutPred		0.25		Gain of MoRF binding (P = 0.0016)
MVP		0.043
MPC		0.69
ClinPred		0.73	D
GERP RS		3.2
PromoterAI		0.017	Neutral
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.7
Varity_R		0.23
gMVP		0.26
Mutation Taster		=63/37	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: rs907641600; hg19: chr19-18530471;