16-3089239-C-G

Position:

• chr16-3089239-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_032805.3(ZSCAN10):​c.2195G>C​(p.Ser732Thr) 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. 15/21 in silico tools predict a benign 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: -0.878

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.075811476).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZSCAN10	NM_032805.3	c.2195G>C	p.Ser732Thr	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.2195G>C	p.Ser732Thr	missense_variant	6/6	5	NM_032805.3	ENSP00000458879	P1
ZSCAN10	ENST00000252463.6	c.2030G>C	p.Ser677Thr	missense_variant	5/5	1		ENSP00000252463
ZSCAN10	ENST00000538082.5	c.1784G>C	p.Ser595Thr	missense_variant	5/5	4		ENSP00000440047
ZSCAN10	ENST00000575108.5	c.1013G>C	p.Ser338Thr	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

Feb 07, 2023

The c.2030G>C (p.S677T) alteration is located in exon 5 (coding exon 5) of the ZSCAN10 gene. This alteration results from a G to C substitution at nucleotide position 2030, causing the serine (S) at amino acid position 677 to be replaced by a threonine (T). 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	Benign	0.079
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	7.6
DANN	Benign	0.88
DEOGEN2	Benign	0.020	T;T;.;.
Eigen	Benign	-0.88
Eigen_PC	Benign	-0.77
FATHMM_MKL	Benign	0.19	N
LIST_S2	Benign	0.60	T;T;T;T
M_CAP	Benign	0.0063	T
MetaRNN	Benign	0.076	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.26	.;N;.;.
MutationTaster	Benign	0.99	N;N;N
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	-1.1	.;N;.;.
REVEL	Benign	0.036
Sift	Benign	0.19	.;T;.;.
Sift4G	Benign	0.29	T;T;T;T
Polyphen		0.0020, 0.0	.;B;B;.
Vest4		0.10
MutPred		0.45		.;Loss of ubiquitination at K676 (P = 0.0853);.;.;
MVP		0.48
MPC		0.72
ClinPred		0.070	T
GERP RS		0.070
Varity_R		0.11
gMVP		0.19

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: chr16-3139240;