16-3089245-C-T

Variant names:

• chr16-3089245-C-T
• rs773482636
• NM_032805.3:c.2189G>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_032805.3(ZSCAN10):​c.2189G>A​(p.Gly730Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000049 in 1,429,872 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. G730A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000049 (0 hom.)
• Consequence: ZSCAN10 NM_032805.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.02
• Publications: 0 publications found

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]

ZSCAN10 Gene-Disease associations (from GenCC):

• otofacial neurodevelopmental syndrome

  Inheritance: AR Classification: MODERATE Submitted by: Ambry Genetics

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032805.3. 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
	ZSCAN10	NM_032805.3	MANE Select	c.2189G>A	p.Gly730Glu	missense	Exon 6 of 6	NP_116194.2	Q96SZ4-1
	ZSCAN10	NM_001282416.2		c.1778G>A	p.Gly593Glu	missense	Exon 5 of 5	NP_001269345.1	Q96SZ4-3
	ZSCAN10	NM_001365272.1		c.1643G>A	p.Gly548Glu	missense	Exon 5 of 5	NP_001352201.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZSCAN10	ENST00000576985.6	TSL:5 MANE Select	c.2189G>A	p.Gly730Glu	missense	Exon 6 of 6	ENSP00000458879.2	I3L1J3
	ZSCAN10	ENST00000252463.6	TSL:1	c.2024G>A	p.Gly675Glu	missense	Exon 5 of 5	ENSP00000252463.2	A0ABB0GZV6
	ZSCAN10	ENST00000538082.5	TSL:4	c.1778G>A	p.Gly593Glu	missense	Exon 5 of 5	ENSP00000440047.2	Q96SZ4-3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000498 AC: 1 AN: 200718 AF XY: 0.00000898

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000111

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000490 AC: 7 AN: 1429872 Hom.: 0 Cov.: 31 AF XY: 0.00000703 AC XY: 5 AN XY: 710972

African (AFR) AF: 0.00 AC: 0 AN: 32478

American (AMR) AF: 0.00 AC: 0 AN: 42222

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24998

East Asian (EAS) AF: 0.00 AC: 0 AN: 38840

South Asian (SAS) AF: 0.00 AC: 0 AN: 83254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39810

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5542

European-Non Finnish (NFE) AF: 0.00000634 AC: 7 AN: 1103342

Other (OTH) AF: 0.00 AC: 0 AN: 59386

GnomAD4 genome Cov.: 33

ExAC AF: 0.00000836 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.64
BayesDel_addAF	Uncertain	0.075	D
BayesDel_noAF	Benign	-0.13
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.088	T
Eigen	Uncertain	0.47
Eigen_PC	Uncertain	0.38
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.59	T
M_CAP	Benign	0.048	D
MetaRNN	Uncertain	0.48	T
MetaSVM	Benign	-0.30	T
MutationAssessor	Benign	1.8	L
PhyloP100		3.0
PrimateAI	Pathogenic	0.85	D
PROVEAN	Pathogenic	-5.4	D
REVEL	Uncertain	0.35
Sift	Benign	0.036	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.58
MutPred		0.59		Gain of ubiquitination at K676 (P = 0.0381)
MVP		0.84
MPC		2.1
ClinPred		0.98	D
GERP RS		4.7
Varity_R		0.47
gMVP		0.40
Mutation Taster		=45/55	disease causing

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: rs773482636; hg19: chr16-3139246;