16-3089551-T-C

Position:

• chr16-3089551-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_032805.3(ZSCAN10):​c.1883A>G​(p.His628Arg) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZSCAN10 NM_032805.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.02

Genes affected

ZSCAN10 (HGNC:12997): (zinc finger and SCAN domain containing 10) 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 negative regulation of transcription, DNA-templated and regulation of transcription by RNA polymerase II. Predicted to be located in nucleoplasm. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.815

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZSCAN10	NM_032805.3	c.1883A>G	p.His628Arg	missense_variant	6/6	ENST00000576985.6	NP_116194.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZSCAN10	ENST00000576985.6	c.1883A>G	p.His628Arg	missense_variant	6/6	5	NM_032805.3	ENSP00000458879	P1
ZSCAN10	ENST00000252463.6	c.1718A>G	p.His573Arg	missense_variant	5/5	1		ENSP00000252463
ZSCAN10	ENST00000538082.5	c.1472A>G	p.His491Arg	missense_variant	5/5	4		ENSP00000440047
ZSCAN10	ENST00000575108.5	c.701A>G	p.His234Arg	missense_variant	5/5	2		ENSP00000459520

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 26, 2022

The c.1718A>G (p.H573R) alteration is located in exon 5 (coding exon 5) of the ZSCAN10 gene. This alteration results from a A to G substitution at nucleotide position 1718, causing the histidine (H) at amino acid position 573 to be replaced by an arginine (R). 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	0.97
BayesDel_addAF	Pathogenic	0.32	D
BayesDel_noAF	Pathogenic	0.22
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.15	T;T;.;.
Eigen	Pathogenic	0.73
Eigen_PC	Uncertain	0.64
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Benign	0.78	T;T;T;T
M_CAP	Uncertain	0.14	D
MetaRNN	Pathogenic	0.82	D;D;D;D
MetaSVM	Uncertain	0.32	D
MutationAssessor	Uncertain	2.3	.;M;.;.
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Pathogenic	0.86	D
PROVEAN	Pathogenic	-7.5	.;D;.;.
REVEL	Pathogenic	0.69
Sift	Pathogenic	0.0	.;D;.;.
Sift4G	Uncertain	0.0040	D;D;D;D
Polyphen		1.0, 1.0	.;D;D;.
Vest4		0.63
MutPred		0.68		.;Gain of MoRF binding (P = 0.0124);.;.;
MVP		0.91
MPC		2.1
ClinPred		1.0	D
GERP RS		5.3
Varity_R		0.87
gMVP		0.50

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-3139552;