chr19-18432054-C-T

Variant names:

• chr19-18432054-C-T
• rs1973433685
• NM_032627.5:c.620C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_032627.5(SSBP4):​c.620C>T​(p.Ala207Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000139 in 1,436,308 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: SSBP4 NM_032627.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.427

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08724734).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SSBP4	NM_032627.5	c.620C>T	p.Ala207Val	missense_variant	Exon 9 of 18	ENST00000270061.12	NP_116016.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SSBP4	ENST00000270061.12	c.620C>T	p.Ala207Val	missense_variant	Exon 9 of 18	1	NM_032627.5	ENSP00000270061.5

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 0.00000139 AC: 2 AN: 1436308 Hom.: 0 Cov.: 37 AF XY: 0.00000141 AC XY: 1 AN XY: 710624

African (AFR) AF: 0.0000303 AC: 1 AN: 33034

American (AMR) AF: 0.00 AC: 0 AN: 43298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24716

East Asian (EAS) AF: 0.00 AC: 0 AN: 39210

South Asian (SAS) AF: 0.00 AC: 0 AN: 83852

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51726

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5642

European-Non Finnish (NFE) AF: 9.13e-7 AC: 1 AN: 1095626

Other (OTH) AF: 0.00 AC: 0 AN: 59204

GnomAD4 genome Cov.: 34

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jul 22, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.620C>T (p.A207V) alteration is located in exon 9 (coding exon 9) of the SSBP4 gene. This alteration results from a C to T substitution at nucleotide position 620, causing the alanine (A) at amino acid position 207 to be replaced by a valine (V). 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	0.099
BayesDel_addAF	Benign	-0.079	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	21
DANN	Benign	0.91
DEOGEN2	Benign	0.0054	T;.;T;.
Eigen	Benign	-0.73
Eigen_PC	Benign	-0.63
FATHMM_MKL	Benign	0.53	D
LIST_S2	Benign	0.77	T;T;T;T
M_CAP	Benign	0.0082	T
MetaRNN	Benign	0.087	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.68	.;.;N;.
PhyloP100		0.43
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-0.80	.;N;N;.
REVEL	Benign	0.19
Sift	Benign	0.54	.;T;T;.
Sift4G	Benign	0.33	T;T;T;T
Polyphen		0.0	.;.;B;.
Vest4		0.46, 0.45
MutPred		0.54		Loss of methylation at R204 (P = 0.0944);.;Loss of methylation at R204 (P = 0.0944);.;
MVP		0.068
MPC		0.24
ClinPred		0.16	T
GERP RS		4.3
PromoterAI		0.011	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.064
gMVP		0.22
Mutation Taster		=62/38	polymorphism

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

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Other links and lift over

dbSNP: rs1973433685; hg19: chr19-18542864;