6-28125822-G-T

Variant names:

• chr6-28125822-G-T
• rs745465985
• NM_025231.3:c.379G>T

Variant summary

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

The NM_025231.3(ZSCAN16):​c.379G>T​(p.Gly127*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000069 in 1,448,520 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: 6.9e-7 (0 hom.)
• Consequence: ZSCAN16 NM_025231.3 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.859
• 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.379G>T	p.Gly127*	stop_gained	Exon 2 of 4	NP_079507.1	Q9H4T2
	ZSCAN16	NM_001320555.2		c.379G>T	p.Gly127*	stop_gained	Exon 2 of 4	NP_001307484.1	Q9H4T2
	ZSCAN16	NM_001320557.2		c.379G>T	p.Gly127*	stop_gained	Exon 2 of 4	NP_001307486.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZSCAN16	ENST00000340487.5	TSL:1 MANE Select	c.379G>T	p.Gly127*	stop_gained	Exon 2 of 4	ENSP00000366527.3	Q9H4T2
	ZSCAN16-AS1	ENST00000602810.3	TSL:1	n.574-2611C>A		intron	N/A
	ZSCAN16	ENST00000685330.1		c.379G>T	p.Gly127*	stop_gained	Exon 2 of 4	ENSP00000510203.1	Q9H4T2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.90e-7 AC: 1 AN: 1448520 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 719656

African (AFR) AF: 0.00 AC: 0 AN: 33154

American (AMR) AF: 0.00 AC: 0 AN: 41852

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25720

East Asian (EAS) AF: 0.00 AC: 0 AN: 39198

South Asian (SAS) AF: 0.00 AC: 0 AN: 84904

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52924

Middle Eastern (MID) AF: 0.000181 AC: 1 AN: 5520

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1105288

Other (OTH) AF: 0.00 AC: 0 AN: 59960

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Uncertain	0.080
CADD	Pathogenic	32
DANN	Benign	0.97
Eigen	Benign	-0.14
Eigen_PC	Benign	-0.58
FATHMM_MKL	Benign	0.019	N
PhyloP100		-0.86
Vest4		0.033
GERP RS		-7.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=102/98	disease causing (fs/PTC)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs745465985; hg19: chr6-28093600;