NM_032805.3:c.1923G>C

Variant names:

• chr16-3089511-C-G
• rs1181662794
• NM_032805.3:c.1923G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_032805.3(ZSCAN10):​c.1923G>C​(p.Glu641Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000312 in 1,601,306 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000028 (0 hom.)
• Consequence: ZSCAN10 NM_032805.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.324
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1719963).

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.1923G>C	p.Glu641Asp	missense	Exon 6 of 6	NP_116194.2	Q96SZ4-1
	ZSCAN10	NM_001282416.2		c.1512G>C	p.Glu504Asp	missense	Exon 5 of 5	NP_001269345.1	Q96SZ4-3
	ZSCAN10	NM_001365272.1		c.1377G>C	p.Glu459Asp	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.1923G>C	p.Glu641Asp	missense	Exon 6 of 6	ENSP00000458879.2	I3L1J3
	ZSCAN10	ENST00000252463.6	TSL:1	c.1758G>C	p.Glu586Asp	missense	Exon 5 of 5	ENSP00000252463.2	A0ABB0GZV6
	ZSCAN10	ENST00000538082.5	TSL:4	c.1512G>C	p.Glu504Asp	missense	Exon 5 of 5	ENSP00000440047.2	Q96SZ4-3

Frequencies

GnomAD3 genomes AF: 0.00000660 AC: 1 AN: 151550 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000243

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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000430 AC: 1 AN: 232584 AF XY: 0.00000784

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: 0.00000961

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000276 AC: 4 AN: 1449756 Hom.: 0 Cov.: 31 AF XY: 0.00000416 AC XY: 3 AN XY: 720920

African (AFR) AF: 0.00 AC: 0 AN: 32954

American (AMR) AF: 0.00 AC: 0 AN: 43208

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25620

East Asian (EAS) AF: 0.00 AC: 0 AN: 39416

South Asian (SAS) AF: 0.00 AC: 0 AN: 85348

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50038

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5738

European-Non Finnish (NFE) AF: 0.00000361 AC: 4 AN: 1107562

Other (OTH) AF: 0.00 AC: 0 AN: 59872

GnomAD4 genome AF: 0.00000660 AC: 1 AN: 151550 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 73998

African (AFR) AF: 0.0000243 AC: 1 AN: 41220

American (AMR) AF: 0.00 AC: 0 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5140

South Asian (SAS) AF: 0.00 AC: 0 AN: 4806

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10538

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67820

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.62
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	9.1
DANN	Uncertain	1.0
DEOGEN2	Benign	0.045	T
Eigen	Benign	-0.18
Eigen_PC	Benign	-0.26
FATHMM_MKL	Benign	0.37	N
LIST_S2	Benign	0.32	T
M_CAP	Benign	0.026	D
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.1	L
PhyloP100		-0.32
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.13
Sift	Benign	0.061	T
Sift4G	Benign	0.17	T
Polyphen		1.0	D
Vest4		0.31
MutPred		0.48		Loss of phosphorylation at S582 (P = 0.1647)
MVP		0.48
MPC		1.8
ClinPred		0.52	D
GERP RS		2.3
Varity_R		0.11
gMVP		0.21
Mutation Taster		=93/7	polymorphism

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: rs1181662794; hg19: chr16-3139512;