19-18431794-C-T

Variant names:

• chr19-18431794-C-T
• rs1973409032
• NM_032627.5:c.497C>T

Variant summary

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

The NM_032627.5(SSBP4):​c.497C>T​(p.Pro166Leu) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000142 in 1,404,152 control chromosomes in the GnomAD database, with no homozygous occurrence. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: SSBP4 NM_032627.5 missense, splice_region
• Scores: Splicing: ADA: 0.7274
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.36
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.497C>T	p.Pro166Leu	missense splice_region	Exon 8 of 18	NP_116016.1	Q9BWG4-1
	SSBP4	NM_001009998.4		c.431C>T	p.Pro144Leu	missense splice_region	Exon 7 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.497C>T	p.Pro166Leu	missense splice_region	Exon 8 of 18	ENSP00000270061.5	Q9BWG4-1
	SSBP4	ENST00000915352.1		c.431C>T	p.Pro144Leu	missense splice_region	Exon 7 of 17	ENSP00000585411.1
	SSBP4	ENST00000867041.1		c.437C>T	p.Pro146Leu	missense splice_region	Exon 7 of 17	ENSP00000537100.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000142 AC: 2 AN: 1404152 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 692858

African (AFR) AF: 0.00 AC: 0 AN: 32018

American (AMR) AF: 0.00 AC: 0 AN: 37372

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25120

East Asian (EAS) AF: 0.0000551 AC: 2 AN: 36330

South Asian (SAS) AF: 0.00 AC: 0 AN: 80234

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48260

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5692

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1081068

Other (OTH) AF: 0.00 AC: 0 AN: 58058

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	0.0025	T
BayesDel_noAF	Benign	-0.23
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.11	T
Eigen	Benign	0.12
Eigen_PC	Benign	0.075
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.039	D
MetaRNN	Uncertain	0.62	D
MetaSVM	Benign	-0.80	T
MutationAssessor	Benign	1.9	L
PhyloP100		2.4
PrimateAI	Uncertain	0.74	T
PROVEAN	Pathogenic	-4.9	D
REVEL	Uncertain	0.40
Sift	Benign	0.085	T
Sift4G	Uncertain	0.049	D
Polyphen		0.96	D
Vest4		0.54
MutPred		0.66		Loss of glycosylation at P166 (P = 0.0424)
MVP		0.068
MPC		0.75
ClinPred		0.98	D
GERP RS		4.0
PromoterAI		0.020	Neutral
Varity_R		0.20
gMVP		0.18
Mutation Taster		=55/45	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.73
dbscSNV1_RF	Benign	0.65
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: rs1973409032; hg19: chr19-18542604;