Genetic Variant SSBP3:p.Pro125Ala (chr1-54258143-G-C) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_145716.4(SSBP3):c.373C>G(p.Pro125Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000207 in 1,591,824 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: 𝑓 0.00014 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000076 ( 0 hom. )

Consequence

SSBP3
NM_145716.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.12

Publications

1 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.14861917).

BS2

High AC in GnomAd4 at 22 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145716.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SSBP3	NM_145716.4	MANE Select	c.373C>G	p.Pro125Ala	missense	Exon 6 of 18	NP_663768.1	Q9BWW4-1
SSBP3	NM_018070.5		c.373C>G	p.Pro125Ala	missense	Exon 6 of 17	NP_060540.2
SSBP3	NM_001394364.1		c.43C>G	p.Pro15Ala	missense	Exon 6 of 18	NP_001381293.1	Q9NW25

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SSBP3	ENST00000610401.6	TSL:5 MANE Select	c.373C>G	p.Pro125Ala	missense	Exon 6 of 18	ENSP00000479674.2	Q9BWW4-1
SSBP3	ENST00000357475.9	TSL:1	c.373C>G	p.Pro125Ala	missense	Exon 6 of 17	ENSP00000350067.4	Q9BWW4-3
SSBP3	ENST00000371320.8	TSL:1	n.640-957C>G		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.000145

AC:

AN:

152086

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000507

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:

0.00

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.0000277

AC:

AN:

216414

AF XY:

0.00000862

show subpopulations

Gnomad AFR exome

AF:

0.000452

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000764

AC:

AN:

1439620

Hom.:

Cov.:

AF XY:

0.00000561

AC XY:

AN XY:

713572

show subpopulations

African (AFR)

AF:

0.000301

AC:

AN:

33172

American (AMR)

AF:

0.00

AC:

AN:

40530

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25548

East Asian (EAS)

AF:

0.00

AC:

AN:

38798

South Asian (SAS)

AF:

0.00

AC:

AN:

81958

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52146

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5678

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1102210

Other (OTH)

AF:

0.0000168

AC:

AN:

59580

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000145

AC:

AN:

152204

Hom.:

Cov.:

AF XY:

0.000175

AC XY:

AN XY:

74434

show subpopulations

African (AFR)

AF:

0.000506

AC:

AN:

41522

American (AMR)

AF:

0.00

AC:

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5164

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10606

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68014

Other (OTH)

AF:

0.000473

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.520

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000214

Hom.:

Bravo

AF:

0.000144

ESP6500AA

AF:

0.000455

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000414

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.063

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.12

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.54

Eigen

Uncertain

0.22

Eigen_PC

Uncertain

0.38

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.90

M_CAP

Benign

0.0023

MetaRNN

Benign

0.15

MetaSVM

Benign

-0.67

MutationAssessor

Uncertain

2.4

PhyloP100

9.1

PrimateAI

Uncertain

0.75

PROVEAN

Uncertain

-2.6

REVEL

Benign

0.19

Sift

Benign

0.041

Sift4G

Uncertain

0.015

Polyphen

0.016

Vest4

0.59

MVP

0.15

MPC

2.0

ClinPred

0.30

GERP RS

5.0

Varity_R

0.20

gMVP

0.52

Mutation Taster

=47/53

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over