1-54405990-C-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_145716.4(SSBP3):​c.19G>A​(p.Gly7Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000673 in 1,486,760 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000067 ( 0 hom., cov: 29)
Exomes 𝑓: 0.0000067 ( 0 hom. )

Consequence

SSBP3
NM_145716.4 missense

Scores

2
2
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.76
Variant links:
Genes affected
SSBP3 (HGNC:15674): (single stranded DNA binding protein 3) Predicted to enable single-stranded DNA binding activity and transcription coactivator activity. Predicted to be involved in head development and positive regulation of transcription by RNA polymerase II. Predicted to act upstream of or within hematopoietic progenitor cell differentiation. Predicted to be part of protein-containing complex. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.16057009).
BS2
High AC in GnomAdExome4 at 9 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SSBP3NM_145716.4 linkc.19G>A p.Gly7Ser missense_variant Exon 1 of 18 NP_663768.1 Q9BWW4-1
SSBP3NM_001394360.1 linkc.19G>A p.Gly7Ser missense_variant Exon 1 of 17 NP_001381289.1
SSBP3NM_018070.5 linkc.19G>A p.Gly7Ser missense_variant Exon 1 of 17 NP_060540.2 Q9BWW4-3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SSBP3ENST00000610401.6 linkc.19G>A p.Gly7Ser missense_variant Exon 1 of 18 5 ENSP00000479674.2 Q9BWW4-1A0A087WVT6
SSBP3ENST00000357475.9 linkc.19G>A p.Gly7Ser missense_variant Exon 1 of 17 1 ENSP00000350067.4 Q9BWW4-3
SSBP3ENST00000371319.8 linkc.19G>A p.Gly7Ser missense_variant Exon 1 of 17 2 ENSP00000360370.3 Q9BWW4-2
SSBP3ENST00000525990.1 linkc.-274-1060G>A intron_variant Intron 1 of 8 2 ENSP00000431654.1 E9PK49

Frequencies

GnomAD3 genomes
AF:
0.00000665
AC:
1
AN:
150286
Hom.:
0
Cov.:
29
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000148
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000734
AC:
1
AN:
136282
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
76372
show subpopulations
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 SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000179
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000673
AC:
9
AN:
1336474
Hom.:
0
Cov.:
31
AF XY:
0.00000302
AC XY:
2
AN XY:
662286
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000315
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:
0.00000765
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000665
AC:
1
AN:
150286
Hom.:
0
Cov.:
29
AF XY:
0.00
AC XY:
0
AN XY:
73352
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000148
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000282
Hom.:
0

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Mar 05, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.19G>A (p.G7S) alteration is located in exon 1 (coding exon 1) of the SSBP3 gene. This alteration results from a G to A substitution at nucleotide position 19, causing the glycine (G) at amino acid position 7 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.11
BayesDel_addAF
Benign
-0.14
T
BayesDel_noAF
Benign
-0.44
CADD
Benign
23
DANN
Uncertain
0.99
DEOGEN2
Benign
0.23
T;.;.
Eigen
Benign
-0.58
Eigen_PC
Benign
-0.41
FATHMM_MKL
Benign
0.50
D
LIST_S2
Uncertain
0.96
D;D;D
M_CAP
Pathogenic
0.87
D
MetaRNN
Benign
0.16
T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
-0.14
N;N;N
PrimateAI
Pathogenic
0.90
D
PROVEAN
Benign
-2.0
N;N;N
REVEL
Benign
0.088
Sift
Benign
0.32
T;T;T
Sift4G
Benign
0.48
T;T;T
Polyphen
0.0010
B;B;B
Vest4
0.20
MutPred
0.077
Gain of phosphorylation at G7 (P = 0.033);Gain of phosphorylation at G7 (P = 0.033);Gain of phosphorylation at G7 (P = 0.033);
MVP
0.043
MPC
1.9
ClinPred
0.55
D
GERP RS
2.6
Varity_R
0.21
gMVP
0.58

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1352002330; hg19: chr1-54871663; API