Variant chr1-54258109-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The ENST00000610401.6(SSBP3):c.407C>T(p.Pro136Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000207 in 1,447,704 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: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

SSBP3
ENST00000610401.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.98

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.28378746).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SSBP3	NM_145716.4 linkuse as main transcript	c.407C>T	p.Pro136Leu	missense_variant	6/18	ENST00000610401.6
SSBP3	NM_001394365.1 linkuse as main transcript	c.37-923C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SSBP3	ENST00000610401.6 linkuse as main transcript	c.407C>T	p.Pro136Leu	missense_variant	6/18	5	NM_145716.4	P1	Q9BWW4-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000207

AC:

AN:

1447704

Hom.:

Cov.:

AF XY:

0.00000278

AC XY:

AN XY:

718346

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

0.00000271

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 06, 2023

The c.407C>T (p.P136L) alteration is located in exon 6 (coding exon 6) of the SSBP3 gene. This alteration results from a C to T substitution at nucleotide position 407, causing the proline (P) at amino acid position 136 to be replaced by a leucine (L). 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

0.12

BayesDel_addAF

Uncertain

0.047

BayesDel_noAF

Benign

-0.17

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.50

.;D;.

Eigen

Uncertain

0.25

Eigen_PC

Uncertain

0.40

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.96

D;D;D

M_CAP

Benign

0.0054

MetaRNN

Benign

0.28

T;T;T

MetaSVM

Benign

-0.62

MutationAssessor

Benign

1.4

.;L;L

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Pathogenic

0.81

PROVEAN

Benign

-2.2

N;N;D

REVEL

Benign

0.22

Sift

Benign

0.047

D;D;D

Sift4G

Benign

0.15

T;T;D

Polyphen

0.071, 0.031

.;B;B

Vest4

0.51

MutPred

0.39

.;Loss of glycosylation at P136 (P = 0.0048);Loss of glycosylation at P136 (P = 0.0048);

MVP

0.043

MPC

1.9

ClinPred

0.97

GERP RS

5.0

Varity_R

0.28

gMVP

0.60

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over