chr19-18431380-C-T

Variant names:

• chr19-18431380-C-T
• rs766718404
• NM_032627.5:c.397C>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.397C>T​(p.His133Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000768 in 1,301,608 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H133N) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 7.7e-7 (0 hom.)
• Consequence: SSBP4 NM_032627.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.18
• Publications: 0 publications found

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=0.17667124).

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.397C>T	p.His133Tyr	missense	Exon 6 of 18	NP_116016.1	Q9BWG4-1
	SSBP4	NM_001009998.4		c.370-267C>T		intron	N/A	NP_001009998.1	Q9BWG4-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SSBP4	ENST00000270061.12	TSL:1 MANE Select	c.397C>T	p.His133Tyr	missense	Exon 6 of 18	ENSP00000270061.5	Q9BWG4-1
	SSBP4	ENST00000867041.1		c.397C>T	p.His133Tyr	missense	Exon 6 of 17	ENSP00000537100.1
	SSBP4	ENST00000915353.1		c.397C>T	p.His133Tyr	missense	Exon 6 of 17	ENSP00000585412.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 7.68e-7 AC: 1 AN: 1301608 Hom.: 0 Cov.: 21 AF XY: 0.00 AC XY: 0 AN XY: 649044

African (AFR) AF: 0.00 AC: 0 AN: 28166

American (AMR) AF: 0.00 AC: 0 AN: 27170

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22808

East Asian (EAS) AF: 0.00 AC: 0 AN: 36866

South Asian (SAS) AF: 0.00 AC: 0 AN: 73676

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49242

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4852

European-Non Finnish (NFE) AF: 9.95e-7 AC: 1 AN: 1004600

Other (OTH) AF: 0.00 AC: 0 AN: 54228

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.096
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	17
DANN	Benign	0.92
DEOGEN2	Benign	0.13	T
Eigen	Benign	-0.32
Eigen_PC	Benign	-0.50
FATHMM_MKL	Benign	0.30	N
LIST_S2	Benign	0.59	T
M_CAP	Benign	0.0025	T
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	1.8	L
PhyloP100		1.2
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.12
Sift	Benign	0.046	D
Sift4G	Uncertain	0.039	D
Polyphen		0.97	D
Vest4		0.25
MutPred		0.48		Gain of phosphorylation at H133 (P = 0.005)
MVP		0.10
MPC		0.36
ClinPred		0.50	T
GERP RS		1.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.3
Varity_R		0.076
gMVP		0.37
Mutation Taster		=88/12	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs766718404; hg19: chr19-18542190;