16-3089328-G-C

Variant names:

• chr16-3089328-G-C
• rs573961182
• NM_032805.3:c.2106C>G

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.2106C>G​(p.Asn702Lys) 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 1,432,666 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: ZSCAN10 NM_032805.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.56
• 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=0.0939914).

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.2106C>G	p.Asn702Lys	missense	Exon 6 of 6	NP_116194.2	Q96SZ4-1
	ZSCAN10	NM_001282416.2		c.1695C>G	p.Asn565Lys	missense	Exon 5 of 5	NP_001269345.1	Q96SZ4-3
	ZSCAN10	NM_001365272.1		c.1560C>G	p.Asn520Lys	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.2106C>G	p.Asn702Lys	missense	Exon 6 of 6	ENSP00000458879.2	I3L1J3
	ZSCAN10	ENST00000252463.6	TSL:1	c.1941C>G	p.Asn647Lys	missense	Exon 5 of 5	ENSP00000252463.2	A0ABB0GZV6
	ZSCAN10	ENST00000538082.5	TSL:4	c.1695C>G	p.Asn565Lys	missense	Exon 5 of 5	ENSP00000440047.2	Q96SZ4-3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.98e-7 AC: 1 AN: 1432666 Hom.: 0 Cov.: 31 AF XY: 0.00000140 AC XY: 1 AN XY: 712122

African (AFR) AF: 0.00 AC: 0 AN: 32586

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

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24988

East Asian (EAS) AF: 0.00 AC: 0 AN: 39298

South Asian (SAS) AF: 0.00 AC: 0 AN: 83854

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40914

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5692

European-Non Finnish (NFE) AF: 9.06e-7 AC: 1 AN: 1103642

Other (OTH) AF: 0.00 AC: 0 AN: 59470

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.81
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	2.1
DANN	Uncertain	0.99
DEOGEN2	Benign	0.018	T
Eigen	Benign	-0.86
Eigen_PC	Benign	-0.93
FATHMM_MKL	Benign	0.18	N
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.094	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	-1.5	N
PhyloP100		-1.6
PrimateAI	Pathogenic	0.88	D
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.15
Sift	Benign	0.32	T
Sift4G	Benign	0.35	T
Polyphen		1.0	D
Vest4		0.25
MutPred		0.39		Gain of catalytic residue at N647 (P = 0.0242)
MVP		0.29
MPC		2.0
ClinPred		0.70	D
GERP RS		-4.5
Varity_R		0.16
gMVP		0.12

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: rs573961182; hg19: chr16-3139329;