16-3089617-T-G

Variant names:

• chr16-3089617-T-G
• NM_032805.3:c.1817A>C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_032805.3(ZSCAN10):​c.1817A>C​(p.His606Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000698 in 1,432,916 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: ZSCAN10 NM_032805.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.09

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.28763786).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZSCAN10	NM_032805.3	c.1817A>C	p.His606Pro	missense_variant	Exon 6 of 6	ENST00000576985.6	NP_116194.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZSCAN10	ENST00000576985.6	c.1817A>C	p.His606Pro	missense_variant	Exon 6 of 6	5	NM_032805.3	ENSP00000458879.2
ZSCAN10	ENST00000252463.6	c.1652A>C	p.His551Pro	missense_variant	Exon 5 of 5	1		ENSP00000252463.2
ZSCAN10	ENST00000538082.5	c.1406A>C	p.His469Pro	missense_variant	Exon 5 of 5	4		ENSP00000440047.2
ZSCAN10	ENST00000575108.5	c.635A>C	p.His212Pro	missense_variant	Exon 5 of 5	2		ENSP00000459520.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.98e-7 AC: 1 AN: 1432916 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 710500

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.11e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jun 07, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1652A>C (p.H551P) alteration is located in exon 5 (coding exon 5) of the ZSCAN10 gene. This alteration results from a A to C substitution at nucleotide position 1652, causing the histidine (H) at amino acid position 551 to be replaced by a proline (P). 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	0.58
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Benign	0.12	T;T;.;.
Eigen	Uncertain	0.35
Eigen_PC	Uncertain	0.24
FATHMM_MKL	Benign	0.29	N
LIST_S2	Benign	0.67	T;T;T;T
M_CAP	Benign	0.060	D
MetaRNN	Benign	0.29	T;T;T;T
MetaSVM	Benign	-0.75	T
MutationAssessor	Uncertain	2.6	.;M;.;.
PrimateAI	Uncertain	0.71	T
PROVEAN	Pathogenic	-5.1	.;D;.;.
REVEL	Benign	0.12
Sift	Uncertain	0.013	.;D;.;.
Sift4G	Uncertain	0.043	D;D;D;D
Polyphen		0.99, 0.97	.;D;D;.
Vest4		0.36
MutPred		0.64		.;Loss of catalytic residue at H551 (P = 0.0431);.;.;
MVP		0.58
MPC		2.3
ClinPred		0.89	D
GERP RS		4.2
Varity_R		0.55
gMVP		0.60

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: chr16-3139618;