16-3089511-C-T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_032805.3(ZSCAN10):​c.1923G>A​(p.Glu641Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000069 in 1,449,756 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: ZSCAN10 NM_032805.3 synonymous
• Clinical Significance: Not reported in ClinVar
• 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BP7: Synonymous conserved (PhyloP=-0.324 with no splicing effect.

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>A	p.Glu641Glu	synonymous	Exon 6 of 6	NP_116194.2	Q96SZ4-1
	ZSCAN10	NM_001282416.2		c.1512G>A	p.Glu504Glu	synonymous	Exon 5 of 5	NP_001269345.1	Q96SZ4-3
	ZSCAN10	NM_001365272.1		c.1377G>A	p.Glu459Glu	synonymous	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>A	p.Glu641Glu	synonymous	Exon 6 of 6	ENSP00000458879.2	I3L1J3
	ZSCAN10	ENST00000252463.6	TSL:1	c.1758G>A	p.Glu586Glu	synonymous	Exon 5 of 5	ENSP00000252463.2	A0ABB0GZV6
	ZSCAN10	ENST00000538082.5	TSL:4	c.1512G>A	p.Glu504Glu	synonymous	Exon 5 of 5	ENSP00000440047.2	Q96SZ4-3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.90e-7 AC: 1 AN: 1449756 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 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: 0.0000200 AC: 1 AN: 50038

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1107562

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

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	0.85
DANN	Benign	0.80
PhyloP100		-0.32

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;