chr7-99621488-G-C

Variant names:

• chr7-99621488-G-C
• rs749364084
• NM_145115.3:c.503G>C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_145115.3(ZSCAN25):​c.503G>C​(p.Gly168Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000036 in 1,582,054 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000033 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000036 (0 hom.)
• Consequence: ZSCAN25 NM_145115.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.68
• Publications: 1 publications found

Genes affected

ZSCAN25 (HGNC:21961): (zinc finger and SCAN domain containing 25) This gene encodes a protein that bears some similarity to zinc finger proteins, which are involved in DNA binding and protein-protein interactions. Multiple alternatively spliced transcript variants have been identified, but the full-length nature for most of them has not been determined. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.055244684).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZSCAN25	NM_145115.3	c.503G>C	p.Gly168Ala	missense_variant	Exon 5 of 8	ENST00000394152.7	NP_660090.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZSCAN25	ENST00000394152.7	c.503G>C	p.Gly168Ala	missense_variant	Exon 5 of 8	5	NM_145115.3	ENSP00000377708.2

Frequencies

GnomAD3 genomes AF: 0.0000328 AC: 5 AN: 152250 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000252 AC: 6 AN: 238442 AF XY: 0.0000232

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000274

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000364 AC: 52 AN: 1429804 Hom.: 0 Cov.: 30 AF XY: 0.0000394 AC XY: 28 AN XY: 710214

African (AFR) AF: 0.00 AC: 0 AN: 32682

American (AMR) AF: 0.00 AC: 0 AN: 42494

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25220

East Asian (EAS) AF: 0.0000263 AC: 1 AN: 38042

South Asian (SAS) AF: 0.000219 AC: 18 AN: 82372

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52704

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5604

European-Non Finnish (NFE) AF: 0.0000256 AC: 28 AN: 1091972

Other (OTH) AF: 0.0000852 AC: 5 AN: 58714

GnomAD4 genome AF: 0.0000328 AC: 5 AN: 152250 Hom.: 0 Cov.: 33 AF XY: 0.0000538 AC XY: 4 AN XY: 74386

African (AFR) AF: 0.00 AC: 0 AN: 41472

American (AMR) AF: 0.00 AC: 0 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5198

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 68050

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.0000868 Hom.: 0

Bravo AF: 0.0000189

ExAC AF: 0.0000165 AC: 2

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 30, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.503G>C (p.G168A) alteration is located in exon 5 (coding exon 2) of the ZSCAN25 gene. This alteration results from a G to C substitution at nucleotide position 503, causing the glycine (G) at amino acid position 168 to be replaced by an alanine (A). 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	Benign	0.15
BayesDel_addAF	Benign	-0.45	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	17
DANN	Benign	0.42
DEOGEN2	Benign	0.0097	T;T;T
Eigen	Benign	-0.61
Eigen_PC	Benign	-0.45
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.71	.;T;T
M_CAP	Benign	0.0049	T
MetaRNN	Benign	0.055	T;T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.37	N;N;.
PhyloP100		1.7
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-0.37	N;N;.
REVEL	Benign	0.034
Sift	Benign	0.27	T;T;.
Sift4G	Benign	0.34	T;T;T
Polyphen		0.018	B;B;.
Vest4		0.16
MutPred		0.23		Loss of loop (P = 0.3664);Loss of loop (P = 0.3664);.;
MVP		0.081
MPC		0.38
ClinPred		0.023	T
GERP RS		2.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.039
gMVP		0.12
Mutation Taster		=92/8	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs749364084; hg19: chr7-99219111;