chr16-3089288-C-T

Variant names:

• chr16-3089288-C-T
• rs571695694
• NM_032805.3:c.2146G>A

Variant summary

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

The NM_032805.3(ZSCAN10):​c.2146G>A​(p.Gly716Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000179 in 1,563,368 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000033 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000016 (0 hom.)
• Consequence: ZSCAN10 NM_032805.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.13

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=0.11649302).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZSCAN10	NM_032805.3	c.2146G>A	p.Gly716Arg	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.2146G>A	p.Gly716Arg	missense_variant	Exon 6 of 6	5	NM_032805.3	ENSP00000458879.2
ZSCAN10	ENST00000252463.6	c.1981G>A	p.Gly661Arg	missense_variant	Exon 5 of 5	1		ENSP00000252463.2
ZSCAN10	ENST00000538082.5	c.1735G>A	p.Gly579Arg	missense_variant	Exon 5 of 5	4		ENSP00000440047.2
ZSCAN10	ENST00000575108.5	c.964G>A	p.Gly322Arg	missense_variant	Exon 5 of 5	2		ENSP00000459520.1

Frequencies

GnomAD3 genomes AF: 0.0000329 AC: 5 AN: 152150 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.0000371 AC: 7 AN: 188494 Hom.: 0 AF XY: 0.0000479 AC XY: 5 AN XY: 104442

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000703

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000434

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000345

Gnomad OTH exome AF: 0.000216

GnomAD4 exome AF: 0.0000163 AC: 23 AN: 1411218 Hom.: 0 Cov.: 31 AF XY: 0.0000186 AC XY: 13 AN XY: 700000

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000256

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000250

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000174

Gnomad4 OTH exome AF: 0.0000171

GnomAD4 genome AF: 0.0000329 AC: 5 AN: 152150 Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2 AN XY: 74330

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000735

Gnomad4 OTH AF: 0.00

Bravo AF: 0.0000340

ExAC AF: 0.0000252 AC: 3

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jul 05, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1981G>A (p.G661R) alteration is located in exon 5 (coding exon 5) of the ZSCAN10 gene. This alteration results from a G to A substitution at nucleotide position 1981, causing the glycine (G) at amino acid position 661 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	Benign	0.16
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	16
DANN	Benign	0.93
DEOGEN2	Benign	0.0096	T;T;.;.
Eigen	Benign	-0.45
Eigen_PC	Benign	-0.54
FATHMM_MKL	Benign	0.056	N
LIST_S2	Benign	0.52	T;T;T;T
M_CAP	Benign	0.0092	T
MetaRNN	Benign	0.12	T;T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.36	.;N;.;.
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-0.77	.;N;.;.
REVEL	Benign	0.089
Sift	Benign	0.052	.;T;.;.
Sift4G	Uncertain	0.018	D;D;D;D
Polyphen		0.96, 0.97	.;D;D;.
Vest4		0.18
MutPred		0.16		.;Gain of solvent accessibility (P = 0.0456);.;.;
MVP		0.44
MPC		0.94
ClinPred		0.14	T
GERP RS		3.1
Varity_R		0.057
gMVP		0.16

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

LitVar

Other links and lift over

dbSNP: rs571695694; hg19: chr16-3139289;