Genetic Variant SSBP3:p.Gly7Ser (chr1-54405990-C-T) – ACMG Classification: Likely_benign (-6 pts)

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

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]

SSBP3 links:

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	Protein	UniProt
SSBP3	NM_145716.4 link	c.19G>A	p.Gly7Ser	missense_variant	Exon 1 of 18	NP_663768.1	Q9BWW4-1
SSBP3	NM_001394360.1 link	c.19G>A	p.Gly7Ser	missense_variant	Exon 1 of 17	NP_001381289.1
SSBP3	NM_018070.5 link	c.19G>A	p.Gly7Ser	missense_variant	Exon 1 of 17	NP_060540.2	Q9BWW4-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	Protein	UniProt
SSBP3	ENST00000610401.6 link	c.19G>A	p.Gly7Ser	missense_variant	Exon 1 of 18	5	ENSP00000479674.2	Q9BWW4-1A0A087WVT6
SSBP3	ENST00000357475.9 link	c.19G>A	p.Gly7Ser	missense_variant	Exon 1 of 17	1	ENSP00000350067.4	Q9BWW4-3
SSBP3	ENST00000371319.8 link	c.19G>A	p.Gly7Ser	missense_variant	Exon 1 of 17	2	ENSP00000360370.3	Q9BWW4-2
SSBP3	ENST00000525990.1 link	c.-274-1060G>A		intron_variant	Intron 1 of 8	2	ENSP00000431654.1	E9PK49

Frequencies

GnomAD3 genomes

AF:

0.00000665

AC:

AN:

150286

Hom.:

Cov.:

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:

AN:

136282

Hom.:

AF XY:

0.00

AC XY:

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:

AN:

1336474

Hom.:

Cov.:

AF XY:

0.00000302

AC XY:

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:

AN:

150286

Hom.:

Cov.:

AF XY:

0.00

AC XY:

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.:

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

BayesDel_noAF

Benign

-0.44

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.23

T;.;.

Eigen

Benign

-0.58

Eigen_PC

Benign

-0.41

FATHMM_MKL

Benign

0.50

LIST_S2

Uncertain

0.96

D;D;D

M_CAP

Pathogenic

0.87

MetaRNN

Benign

0.16

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.14

N;N;N

PrimateAI

Pathogenic

0.90

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

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over