chr7-99621409-G-A

Variant names:

• chr7-99621409-G-A
• rs200781115
• NM_145115.3:c.424G>A

Variant summary

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

The NM_145115.3(ZSCAN25):​c.424G>A​(p.Ala142Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000113 in 1,499,518 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000052 (0 hom.)
• Consequence: ZSCAN25 NM_145115.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.867
• Publications: 0 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=0.033415407).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZSCAN25	NM_145115.3	c.424G>A	p.Ala142Thr	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.424G>A	p.Ala142Thr	missense_variant	Exon 5 of 8	5	NM_145115.3	ENSP00000377708.2

Frequencies

GnomAD3 genomes AF: 0.0000657 AC: 10 AN: 152270 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000523

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: 0.00

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.0000103 AC: 2 AN: 194992 AF XY: 0.0000190

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: 0.00

Gnomad OTH exome AF: 0.000455

GnomAD4 exome AF: 0.00000520 AC: 7 AN: 1347130 Hom.: 0 Cov.: 30 AF XY: 0.00000301 AC XY: 2 AN XY: 664378

African (AFR) AF: 0.00 AC: 0 AN: 30074

American (AMR) AF: 0.000117 AC: 4 AN: 34096

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21474

East Asian (EAS) AF: 0.00 AC: 0 AN: 35248

South Asian (SAS) AF: 0.00 AC: 0 AN: 69856

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50114

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5242

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1046300

Other (OTH) AF: 0.0000548 AC: 3 AN: 54726

GnomAD4 genome AF: 0.0000656 AC: 10 AN: 152388 Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3 AN XY: 74520

African (AFR) AF: 0.0000240 AC: 1 AN: 41588

American (AMR) AF: 0.000522 AC: 8 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68050

Other (OTH) AF: 0.000473 AC: 1 AN: 2116

Alfa AF: 0.0000681 Hom.: 0

Bravo AF: 0.000151

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jun 10, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.424G>A (p.A142T) alteration is located in exon 5 (coding exon 2) of the ZSCAN25 gene. This alteration results from a G to A substitution at nucleotide position 424, causing the alanine (A) at amino acid position 142 to be replaced by a threonine (T). 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	0.13
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Benign	0.018	T;T;T
Eigen	Benign	-0.34
Eigen_PC	Benign	-0.18
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.58	.;T;T
M_CAP	Benign	0.0039	T
MetaRNN	Benign	0.033	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N;N;.
PhyloP100		0.87
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-0.35	N;N;.
REVEL	Benign	0.010
Sift	Benign	0.25	T;T;.
Sift4G	Benign	0.39	T;T;T
Polyphen		0.016	B;B;.
Vest4		0.17
MutPred		0.25		Gain of phosphorylation at A142 (P = 0.0311);Gain of phosphorylation at A142 (P = 0.0311);.;
MVP		0.092
MPC		0.26
ClinPred		0.072	T
GERP RS		3.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.033
gMVP		0.18
Mutation Taster		=80/20	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: rs200781115; hg19: chr7-99219032;