19-58085182-C-T

Variant names:

• chr19-58085182-C-T
• NM_001145543.2:c.1036G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001145543.2(ZSCAN18):​c.1036G>A​(p.Ala346Thr) 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. 16/22 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: ZSCAN18 NM_001145543.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.70
• Publications: 0 publications found

Genes affected

ZSCAN18 (HGNC:21037): (zinc finger and SCAN domain containing 18) 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]

ZNF135 (HGNC:12919): (zinc finger protein 135) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Involved in cytoskeleton organization and regulation of cell morphogenesis. 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=0.06830254).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001145543.2. 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
	ZSCAN18	NM_001145543.2	MANE Select	c.1036G>A	p.Ala346Thr	missense	Exon 7 of 7	NP_001139015.1	Q8TBC5-1
	ZSCAN18	NM_001145542.1		c.1204G>A	p.Ala402Thr	missense	Exon 7 of 7	NP_001139014.1	Q8TBC5-3
	ZSCAN18	NM_023926.5		c.1036G>A	p.Ala346Thr	missense	Exon 7 of 7	NP_076415.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZSCAN18	ENST00000601144.6	TSL:1 MANE Select	c.1036G>A	p.Ala346Thr	missense	Exon 7 of 7	ENSP00000468934.1	Q8TBC5-1
	ZSCAN18	ENST00000240727.10	TSL:1	c.1036G>A	p.Ala346Thr	missense	Exon 7 of 7	ENSP00000240727.5	Q8TBC5-1
	ZSCAN18	ENST00000433686.6	TSL:1	c.727G>A	p.Ala243Thr	missense	Exon 6 of 6	ENSP00000412253.2	A0A0C4DG78

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

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	0.085
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	3.7
DANN	Benign	0.97
DEOGEN2	Benign	0.0051	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.038	N
LIST_S2	Benign	0.52	T
M_CAP	Benign	0.0037	T
MetaRNN	Benign	0.068	T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	0.34	N
PhyloP100		1.7
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-0.17	N
REVEL	Benign	0.017
Sift	Benign	0.42	T
Sift4G	Benign	0.37	T
Polyphen		0.035	B
Vest4		0.046
MutPred		0.20		Gain of glycosylation at A346 (P = 0.0243)
MVP		0.11
MPC		0.067
ClinPred		0.062	T
GERP RS		-0.24
Varity_R		0.039
gMVP		0.26
Mutation Taster		=96/4	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

hg19: chr19-58596549;