6-28125606-C-T

Variant names:

• chr6-28125606-C-T
• NM_025231.3:c.163C>T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_025231.3(ZSCAN16):​c.163C>T​(p.Pro55Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZSCAN16 NM_025231.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.38

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZSCAN16	NM_025231.3	c.163C>T	p.Pro55Ser	missense_variant	Exon 2 of 4	ENST00000340487.5	NP_079507.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZSCAN16	ENST00000340487.5	c.163C>T	p.Pro55Ser	missense_variant	Exon 2 of 4	1	NM_025231.3	ENSP00000366527.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 23, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.163C>T (p.P55S) alteration is located in exon 2 (coding exon 1) of the ZSCAN16 gene. This alteration results from a C to T substitution at nucleotide position 163, causing the proline (P) at amino acid position 55 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.69
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Uncertain	24
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.24	T
Eigen	Uncertain	0.57
Eigen_PC	Uncertain	0.37
FATHMM_MKL	Benign	0.29	N
LIST_S2	Pathogenic	0.98	D
M_CAP	Benign	0.0039	T
MetaRNN	Uncertain	0.63	D
MetaSVM	Benign	-0.72	T
MutationAssessor	Pathogenic	3.8	H
PrimateAI	Uncertain	0.56	T
PROVEAN	Pathogenic	-7.0	D
REVEL	Benign	0.17
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.32
MutPred		0.77		Gain of loop (P = 0.0097);
MVP		0.42
MPC		0.58
ClinPred		0.98	D
GERP RS		4.1
Varity_R		0.83
gMVP		0.58

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-28093384;