19-58084919-G-T

Variant names:

• chr19-58084919-G-T
• NM_001145543.2:c.1299C>A
• ZSCAN18 p.Ser433Arg

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001145543.2(ZSCAN18):​c.1299C>A​(p.Ser433Arg) 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. 15/22 in silico tools predict 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. S433G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ZSCAN18 NM_001145543.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.06
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05324191).

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.1299C>A	p.Ser433Arg	missense	Exon 7 of 7	NP_001139015.1	Q8TBC5-1
	ZSCAN18	NM_001145542.1		c.1467C>A	p.Ser489Arg	missense	Exon 7 of 7	NP_001139014.1	Q8TBC5-3
	ZSCAN18	NM_023926.5		c.1299C>A	p.Ser433Arg	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.1299C>A	p.Ser433Arg	missense	Exon 7 of 7	ENSP00000468934.1	Q8TBC5-1
	ZSCAN18	ENST00000240727.10	TSL:1	c.1299C>A	p.Ser433Arg	missense	Exon 7 of 7	ENSP00000240727.5	Q8TBC5-1
	ZSCAN18	ENST00000433686.6	TSL:1	c.990C>A	p.Ser330Arg	missense	Exon 6 of 6	ENSP00000412253.2	A0A0C4DG78

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1443570 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 716920

African (AFR) AF: 0.00 AC: 0 AN: 33290

American (AMR) AF: 0.00 AC: 0 AN: 41954

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25626

East Asian (EAS) AF: 0.00 AC: 0 AN: 39018

South Asian (SAS) AF: 0.00 AC: 0 AN: 83844

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49008

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5744

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1105350

Other (OTH) AF: 0.00 AC: 0 AN: 59736

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.58
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.78
CADD	Benign	2.1
DANN	Benign	0.79
DEOGEN2	Benign	0.0028	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.053	N
LIST_S2	Benign	0.053	T
M_CAP	Benign	0.0058	T
MetaRNN	Benign	0.053	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	-0.95	N
PhyloP100		-2.1
PrimateAI	Benign	0.38	T
PROVEAN	Benign	1.4	N
REVEL	Benign	0.081
Sift	Benign	0.84	T
Sift4G	Benign	1.0	T
Varity_R		0.032
gMVP		0.085
Mutation Taster		=99/1	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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr19-58596286;