Genetic Variant SSBP4:p.Gly5Arg (chr19-18419661-G-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_032627.5(SSBP4):c.13G>A(p.Gly5Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000915 in 1,092,310 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 9.2e-7 ( 0 hom. )

Consequence

SSBP4
NM_032627.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.45

Publications

0 publications found

Variant links:

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]

SSBP4 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.042961597).

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>A	p.Gly5Arg	missense	Exon 1 of 18	NP_116016.1	Q9BWG4-1
	SSBP4	NM_001009998.4		c.13G>A	p.Gly5Arg	missense	Exon 1 of 17	NP_001009998.1	Q9BWG4-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SSBP4	ENST00000270061.12	TSL:1 MANE Select	c.13G>A	p.Gly5Arg	missense	Exon 1 of 18	ENSP00000270061.5	Q9BWG4-1
SSBP4	ENST00000915352.1		c.13G>A	p.Gly5Arg	missense	Exon 1 of 17	ENSP00000585411.1
SSBP4	ENST00000867041.1		c.13G>A	p.Gly5Arg	missense	Exon 1 of 17	ENSP00000537100.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.000788

AC:

AN:

10146

AF XY:

0.000938

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00315

Gnomad ASJ exome

AF:

0.000990

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000769

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

9.15e-7

AC:

AN:

1092310

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

528862

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

21300

American (AMR)

AF:

0.00

AC:

AN:

7962

Ashkenazi Jewish (ASJ)

AF:

0.0000755

AC:

AN:

13244

East Asian (EAS)

AF:

0.00

AC:

AN:

21666

South Asian (SAS)

AF:

0.00

AC:

AN:

38360

European-Finnish (FIN)

AF:

0.00

AC:

AN:

23368

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3932

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

920812

Other (OTH)

AF:

0.00

AC:

AN:

41666

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.225

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

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.79

BayesDel_addAF

Benign

-0.0078

BayesDel_noAF

Benign

-0.25

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.033

Eigen

Benign

0.16

Eigen_PC

Benign

0.18

FATHMM_MKL

Benign

0.45

LIST_S2

Benign

0.69

M_CAP

Pathogenic

0.70

MetaRNN

Benign

0.043

MetaSVM

Benign

-0.61

MutationAssessor

Benign

0.69

PhyloP100

2.5

PrimateAI

Pathogenic

0.92

PROVEAN

Benign

-0.74

REVEL

Benign

0.090

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.0020

Polyphen

0.83

Vest4

0.18

MutPred

0.25

Gain of MoRF binding (P = 0.0016)

MVP

0.043

MPC

0.69

ClinPred

0.11

GERP RS

3.2

PromoterAI

0.038

Neutral

(source)

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.7

Varity_R

0.23

gMVP

0.26

Mutation Taster

=63/37

polymorphism

(source)

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

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over