19-56190117-C-G

Variant names:

• chr19-56190117-C-G
• rs2032705615
• NM_001080456.5:c.1198G>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001080456.5(ZSCAN5B):​c.1198G>C​(p.Val400Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZSCAN5B NM_001080456.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.290

Genes affected

ZSCAN5B (HGNC:34246): (zinc finger and SCAN domain containing 5B) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11500901).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZSCAN5B	NM_001080456.5	c.1198G>C	p.Val400Leu	missense_variant	Exon 5 of 5	ENST00000586855.7	NP_001073925.2
ZSCAN5B	NM_001385638.1	c.1198G>C	p.Val400Leu	missense_variant	Exon 5 of 5		NP_001372567.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZSCAN5B	ENST00000586855.7	c.1198G>C	p.Val400Leu	missense_variant	Exon 5 of 5	5	NM_001080456.5	ENSP00000466072.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 15, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1198G>C (p.V400L) alteration is located in exon 4 (coding exon 4) of the ZSCAN5B gene. This alteration results from a G to C substitution at nucleotide position 1198, causing the valine (V) at amino acid position 400 to be replaced by a leucine (L). 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	Pathogenic	0.69
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	13
DANN	Benign	0.78
DEOGEN2	Benign	0.0029	T;T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.049	N
LIST_S2	Benign	0.50	.;T
M_CAP	Benign	0.00068	T
MetaRNN	Benign	0.12	T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.23	N;N
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-1.6	.;N
REVEL	Benign	0.021
Sift	Benign	0.044	.;D
Sift4G	Benign	0.19	T;T
Polyphen		0.0050	B;B
Vest4		0.16
MutPred		0.22		Loss of MoRF binding (P = 0.1235);Loss of MoRF binding (P = 0.1235);
MVP		0.15
MPC		0.013
ClinPred		0.044	T
GERP RS		0.98
Varity_R		0.073
gMVP		0.18

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

Publications

LitVar

Other links and lift over

dbSNP: rs2032705615; hg19: chr19-56701486;