19-18427954-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_032627.5(SSBP4):​c.251C>T​(p.Ser84Phe) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Consequence

SSBP4
NM_032627.5 missense

Scores

6
10
3

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.61
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.787

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SSBP4NM_032627.5 linkc.251C>T p.Ser84Phe missense_variant Exon 4 of 18 ENST00000270061.12 NP_116016.1 Q9BWG4-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SSBP4ENST00000270061.12 linkc.251C>T p.Ser84Phe missense_variant Exon 4 of 18 1 NM_032627.5 ENSP00000270061.5 Q9BWG4-1

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
Cov.:
38
GnomAD4 genome
Cov.:
31

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Feb 07, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.251C>T (p.S84F) alteration is located in exon 4 (coding exon 4) of the SSBP4 gene. This alteration results from a C to T substitution at nucleotide position 251, causing the serine (S) at amino acid position 84 to be replaced by a phenylalanine (F). 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
Pathogenic
0.98
BayesDel_addAF
Pathogenic
0.17
D
BayesDel_noAF
Uncertain
0.0
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Benign
0.39
T;.;T
Eigen
Uncertain
0.47
Eigen_PC
Uncertain
0.38
FATHMM_MKL
Uncertain
0.82
D
LIST_S2
Pathogenic
0.99
D;D;D
M_CAP
Benign
0.026
D
MetaRNN
Pathogenic
0.79
D;D;D
MetaSVM
Uncertain
-0.20
T
MutationAssessor
Uncertain
2.5
.;M;M
PrimateAI
Uncertain
0.53
T
PROVEAN
Uncertain
-4.3
.;D;D
REVEL
Uncertain
0.33
Sift
Pathogenic
0.0
.;D;D
Sift4G
Pathogenic
0.0
D;D;D
Polyphen
0.96
.;.;D
Vest4
0.53, 0.54
MutPred
0.68
.;Loss of glycosylation at S84 (P = 0.0012);Loss of glycosylation at S84 (P = 0.0012);
MVP
0.093
MPC
0.74
ClinPred
0.99
D
GERP RS
3.7
Varity_R
0.70
gMVP
0.57

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-18538764; API