6-28125705-C-T

Variant names:

• chr6-28125705-C-T
• rs375022758
• NM_025231.3:c.262C>T

Variant summary

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

The NM_025231.3(ZSCAN16):​c.262C>T​(p.Gln88*) variant causes a stop gained change. The variant allele was found at a frequency of 0.000000684 in 1,461,894 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ZSCAN16 NM_025231.3 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.58
• Publications: 0 publications found

Genes affected

ZSCAN16 (HGNC:20813): (zinc finger and SCAN domain containing 16) Enables sequence-specific double-stranded DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZSCAN16-AS1 (HGNC:48982): (ZSCAN16 antisense RNA 1)

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_025231.3. 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
	ZSCAN16	NM_025231.3	MANE Select	c.262C>T	p.Gln88*	stop_gained	Exon 2 of 4	NP_079507.1	Q9H4T2
	ZSCAN16	NM_001320555.2		c.262C>T	p.Gln88*	stop_gained	Exon 2 of 4	NP_001307484.1	Q9H4T2
	ZSCAN16	NM_001320556.2		c.262C>T	p.Gln88*	stop_gained	Exon 2 of 4	NP_001307485.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZSCAN16	ENST00000340487.5	TSL:1 MANE Select	c.262C>T	p.Gln88*	stop_gained	Exon 2 of 4	ENSP00000366527.3	Q9H4T2
	ZSCAN16-AS1	ENST00000602810.3	TSL:1	n.574-2494G>A		intron	N/A
	ZSCAN16	ENST00000685330.1		c.262C>T	p.Gln88*	stop_gained	Exon 2 of 4	ENSP00000510203.1	Q9H4T2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461894 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727248

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1112012

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.57	D
BayesDel_noAF	Pathogenic	0.59
CADD	Pathogenic	37
DANN	Uncertain	1.0
Eigen	Pathogenic	0.97
Eigen_PC	Pathogenic	0.78
FATHMM_MKL	Uncertain	0.93	D
PhyloP100		4.6
Vest4		0.039
GERP RS		4.0
Mutation Taster		=74/126	disease causing (fs/PTC)

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: rs375022758; hg19: chr6-28093483;