19-18431680-C-G

Variant names:

• chr19-18431680-C-G
• rs778835993
• NM_032627.5:c.469C>G

Variant summary

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

The NM_032627.5(SSBP4):​c.469C>G​(p.Arg157Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000214 in 1,400,550 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 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. R157W) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: SSBP4 NM_032627.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.06

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

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=0.23619005).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SSBP4	NM_032627.5	c.469C>G	p.Arg157Gly	missense_variant	Exon 7 of 18	ENST00000270061.12	NP_116016.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SSBP4	ENST00000270061.12	c.469C>G	p.Arg157Gly	missense_variant	Exon 7 of 18	1	NM_032627.5	ENSP00000270061.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.0000192 AC: 3 AN: 155998 Hom.: 0 AF XY: 0.0000119 AC XY: 1 AN XY: 84132

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000256

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000214 AC: 3 AN: 1400550 Hom.: 0 Cov.: 33 AF XY: 0.00000145 AC XY: 1 AN XY: 691306

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000554

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.25e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000282 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.45
BayesDel_addAF	Uncertain	0.013	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.22	T;.;T;.;.
Eigen	Benign	-0.14
Eigen_PC	Benign	-0.066
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Uncertain	0.86	D;D;D;D;D
M_CAP	Benign	0.050	D
MetaRNN	Benign	0.24	T;T;T;T;T
MetaSVM	Benign	-0.71	T
MutationAssessor	Uncertain	2.2	.;.;M;.;.
PrimateAI	Uncertain	0.75	T
PROVEAN	Pathogenic	-5.8	.;D;D;.;.
REVEL	Benign	0.21
Sift	Uncertain	0.0070	.;D;D;.;.
Sift4G	Uncertain	0.046	D;T;T;D;D
Polyphen		0.0030	.;.;B;.;.
Vest4		0.49, 0.44
MutPred		0.54		Loss of methylation at R157 (P = 0.0231);.;Loss of methylation at R157 (P = 0.0231);.;.;
MVP		0.068
MPC		0.45
ClinPred		0.52	D
GERP RS		3.4
Varity_R		0.70
gMVP		0.40

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

LitVar

Other links and lift over

dbSNP: rs778835993; hg19: chr19-18542490;