19-18419661-G-T

Variant names:

• chr19-18419661-G-T
• rs907641600
• NM_032627.5:c.13G>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_032627.5(SSBP4):​c.13G>T​(p.Gly5Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000129 in 1,241,612 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. G5R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000067 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000014 (0 hom.)
• Consequence: SSBP4 NM_032627.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.45
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2891513).

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.13G>T	p.Gly5Trp	missense	Exon 1 of 18	NP_116016.1	Q9BWG4-1
	SSBP4	NM_001009998.4		c.13G>T	p.Gly5Trp	missense	Exon 1 of 17	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.13G>T	p.Gly5Trp	missense	Exon 1 of 18	ENSP00000270061.5	Q9BWG4-1
	SSBP4	ENST00000915352.1		c.13G>T	p.Gly5Trp	missense	Exon 1 of 17	ENSP00000585411.1
	SSBP4	ENST00000867041.1		c.13G>T	p.Gly5Trp	missense	Exon 1 of 17	ENSP00000537100.1

Frequencies

GnomAD3 genomes AF: 0.00000670 AC: 1 AN: 149302 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000150

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000137 AC: 15 AN: 1092310 Hom.: 0 Cov.: 31 AF XY: 0.0000170 AC XY: 9 AN XY: 528862

African (AFR) AF: 0.0000469 AC: 1 AN: 21300

American (AMR) AF: 0.00 AC: 0 AN: 7962

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13244

East Asian (EAS) AF: 0.00 AC: 0 AN: 21666

South Asian (SAS) AF: 0.00 AC: 0 AN: 38360

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 23368

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3932

European-Non Finnish (NFE) AF: 0.0000141 AC: 13 AN: 920812

Other (OTH) AF: 0.0000240 AC: 1 AN: 41666

GnomAD4 genome AF: 0.00000670 AC: 1 AN: 149302 Hom.: 0 Cov.: 31 AF XY: 0.0000137 AC XY: 1 AN XY: 72770

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 41116

American (AMR) AF: 0.00 AC: 0 AN: 15042

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3422

East Asian (EAS) AF: 0.00 AC: 0 AN: 5126

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000150 AC: 1 AN: 66864

Other (OTH) AF: 0.00 AC: 0 AN: 2058

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.65
BayesDel_addAF	Uncertain	0.042	T
BayesDel_noAF	Benign	-0.18
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Benign	0.063	T
Eigen	Uncertain	0.38
Eigen_PC	Uncertain	0.34
FATHMM_MKL	Benign	0.52	D
LIST_S2	Benign	0.80	T
M_CAP	Pathogenic	0.61	D
MetaRNN	Benign	0.29	T
MetaSVM	Benign	-0.50	T
MutationAssessor	Benign	0.69	N
PhyloP100		2.5
PrimateAI	Pathogenic	0.92	D
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.17
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.34
MutPred		0.26		Gain of MoRF binding (P = 0.0046)
MVP		0.043
MPC		0.79
ClinPred		0.69	D
GERP RS		3.2
PromoterAI		-0.0031	Neutral
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.7
Varity_R		0.21
gMVP		0.31
Mutation Taster		=59/41	polymorphism

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

Other links and lift over

dbSNP: rs907641600; hg19: chr19-18530471;