chr19-56190117-C-G

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 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. 14/22 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
• Publications: 0 publications found

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

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=0.11500901).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001080456.5. 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
	ZSCAN5B	NM_001080456.5	MANE Select	c.1198G>C	p.Val400Leu	missense	Exon 5 of 5	NP_001073925.2	A6NJL1
	ZSCAN5B	NM_001385638.1		c.1198G>C	p.Val400Leu	missense	Exon 5 of 5	NP_001372567.1	A6NJL1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZSCAN5B	ENST00000586855.7	TSL:5 MANE Select	c.1198G>C	p.Val400Leu	missense	Exon 5 of 5	ENSP00000466072.2	A6NJL1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

EpiCase AF: 0.0000545

EpiControl AF: 0.00

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	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
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
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.23	N
PhyloP100		0.29
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.021
Sift	Benign	0.044	D
Sift4G	Benign	0.19	T
Polyphen		0.0050	B
Vest4		0.16
MutPred		0.22		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
Mutation Taster		=100/0	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: rs2032705615; hg19: chr19-56701486;