chr1-54257165-C-T

Variant names:

• chr1-54257165-C-T
• rs201068286
• ENST00000610401.6:c.469G>A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_145716.4(SSBP3):​c.469G>A​(p.Ala157Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00033 in 1,601,996 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 0.00033 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00033 (0 hom.)
• Consequence: SSBP3 NM_145716.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.92

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]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.052152872).
• BS2: High AC in GnomAd4 at 51 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SSBP3	NM_145716.4	c.469G>A	p.Ala157Thr	missense_variant	Exon 7 of 18		NP_663768.1
SSBP3	NM_001394360.1	c.388G>A	p.Ala130Thr	missense_variant	Exon 6 of 17		NP_001381289.1
SSBP3	NM_001009955.4	c.388G>A	p.Ala130Thr	missense_variant	Exon 6 of 17		NP_001009955.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SSBP3	ENST00000610401.6	c.469G>A	p.Ala157Thr	missense_variant	Exon 7 of 18	5		ENSP00000479674.2

Frequencies

GnomAD3 genomes AF: 0.000335 AC: 51 AN: 152192 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000265

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000589

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000471

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000353

Gnomad OTH AF: 0.000957

GnomAD3 exomes AF: 0.000370 AC: 88 AN: 238106 Hom.: 0 AF XY: 0.000317 AC XY: 41 AN XY: 129184

Gnomad AFR exome AF: 0.000195

Gnomad AMR exome AF: 0.000161

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.000559

Gnomad NFE exome AF: 0.000593

Gnomad OTH exome AF: 0.000528

GnomAD4 exome AF: 0.000329 AC: 477 AN: 1449686 Hom.: 0 Cov.: 31 AF XY: 0.000293 AC XY: 211 AN XY: 721010

Gnomad4 AFR exome AF: 0.000213

Gnomad4 AMR exome AF: 0.000142

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000120

Gnomad4 FIN exome AF: 0.000713

Gnomad4 NFE exome AF: 0.000363

Gnomad4 OTH exome AF: 0.000384

GnomAD4 genome AF: 0.000335 AC: 51 AN: 152310 Hom.: 0 Cov.: 32 AF XY: 0.000376 AC XY: 28 AN XY: 74482

Gnomad4 AFR AF: 0.000265

Gnomad4 AMR AF: 0.000588

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000471

Gnomad4 NFE AF: 0.000353

Gnomad4 OTH AF: 0.000947

Alfa AF: 0.000344 Hom.: 0

Bravo AF: 0.000374

TwinsUK AF: 0.000539 AC: 2

ALSPAC AF: 0.000519 AC: 2

ESP6500AA AF: 0.000454 AC: 2

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000469 AC: 57

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 26, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.469G>A (p.A157T) alteration is located in exon 7 (coding exon 7) of the SSBP3 gene. This alteration results from a G to A substitution at nucleotide position 469, causing the alanine (A) at amino acid position 157 to be replaced by a threonine (T). 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	Benign	-0.23	T
BayesDel_noAF	Benign	-0.20
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.018	T;.;T;.;.
Eigen	Uncertain	0.33
Eigen_PC	Uncertain	0.36
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Uncertain	0.86	D;D;D;D;D
M_CAP	Benign	0.0071	T
MetaRNN	Benign	0.052	T;T;T;T;T
MetaSVM	Benign	-0.80	T
MutationAssessor	Benign	1.2	.;.;L;.;.
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	-1.1	.;N;N;N;N
REVEL	Benign	0.17
Sift	Uncertain	0.023	.;D;D;D;D
Sift4G	Benign	0.20	T;T;T;T;D
Polyphen		0.92, 0.98	.;.;P;D;.
Vest4		0.56, 0.41, 0.43
MVP		0.10
MPC		0.90
ClinPred		0.022	T
GERP RS		4.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.19
gMVP		0.34

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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

Other links and lift over

dbSNP: rs201068286; hg19: chr1-54722838;