19-58335086-A-C

Variant names:

• chr19-58335086-A-C
• rs571809706
• NM_181846.3:c.284A>C

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_181846.3(ZSCAN22):​c.284A>C​(p.Glu95Ala) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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. E95V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZSCAN22 NM_181846.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.19
• Publications: 0 publications found

Genes affected

ZSCAN22 (HGNC:4929): (zinc finger and SCAN domain containing 22) 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: Likely_pathogenic. The variant received 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.972

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_181846.3. 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
	ZSCAN22	NM_181846.3	MANE Select	c.284A>C	p.Glu95Ala	missense	Exon 2 of 3	NP_862829.1	P10073
	ZSCAN22	NM_001321116.2		c.284A>C	p.Glu95Ala	missense	Exon 2 of 3	NP_001308045.1	P10073
	ZSCAN22	NM_001321117.2		c.284A>C	p.Glu95Ala	missense	Exon 2 of 3	NP_001308046.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZSCAN22	ENST00000329665.5	TSL:1 MANE Select	c.284A>C	p.Glu95Ala	missense	Exon 2 of 3	ENSP00000332433.3	P10073
	ZSCAN22	ENST00000850584.1		c.284A>C	p.Glu95Ala	missense	Exon 2 of 3	ENSP00000520871.1	P10073
	ZSCAN22	ENST00000904370.1		c.284A>C	p.Glu95Ala	missense	Exon 2 of 3	ENSP00000574429.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.91
BayesDel_addAF	Uncertain	0.026	T
BayesDel_noAF	Benign	-0.20
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.28	T
Eigen	Pathogenic	0.84
Eigen_PC	Pathogenic	0.70
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Benign	0.014	T
MetaRNN	Pathogenic	0.97	D
MetaSVM	Benign	-0.52	T
MutationAssessor	Pathogenic	3.7	H
PhyloP100		5.2
PrimateAI	Uncertain	0.70	T
PROVEAN	Pathogenic	-5.1	D
REVEL	Uncertain	0.36
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.71
MutPred		0.93		Loss of stability (P = 0.3401)
MVP		0.47
MPC		0.55
ClinPred		0.99	D
GERP RS		4.3
Varity_R		0.58
gMVP		0.43
Mutation Taster		=83/17	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: rs571809706; hg19: chr19-58846452; COSMIC: COSV61639205; COSMIC: COSV61639205;