NM_145115.3:c.572G>A

Variant names:

• chr7-99621557-G-A
• rs377391758
• NM_145115.3:c.572G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_145115.3(ZSCAN25):​c.572G>A​(p.Arg191Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000454 in 1,474,546 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 Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000092 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000040 (0 hom.)
• Consequence: ZSCAN25 NM_145115.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.339
• 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.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.029201686).
• BP6: Variant 7-99621557-G-A is Benign according to our data. Variant chr7-99621557-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3990471.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZSCAN25	NM_145115.3	c.572G>A	p.Arg191Gln	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.572G>A	p.Arg191Gln	missense_variant	Exon 5 of 8	5	NM_145115.3	ENSP00000377708.2

Frequencies

GnomAD3 genomes AF: 0.0000920 AC: 14 AN: 152224 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.0000589 AC: 11 AN: 186614 AF XY: 0.0000882

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: 0.000158

Gnomad NFE exome AF: 0.0000916

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000401 AC: 53 AN: 1322322 Hom.: 0 Cov.: 30 AF XY: 0.0000446 AC XY: 29 AN XY: 650486

African (AFR) AF: 0.0000337 AC: 1 AN: 29694

American (AMR) AF: 0.0000903 AC: 3 AN: 33238

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21694

East Asian (EAS) AF: 0.00 AC: 0 AN: 34464

South Asian (SAS) AF: 0.0000150 AC: 1 AN: 66696

European-Finnish (FIN) AF: 0.0000613 AC: 3 AN: 48936

Middle Eastern (MID) AF: 0.000218 AC: 1 AN: 4582

European-Non Finnish (NFE) AF: 0.0000418 AC: 43 AN: 1029684

Other (OTH) AF: 0.0000187 AC: 1 AN: 53334

GnomAD4 genome AF: 0.0000920 AC: 14 AN: 152224 Hom.: 0 Cov.: 33 AF XY: 0.0000807 AC XY: 6 AN XY: 74366

African (AFR) AF: 0.000121 AC: 5 AN: 41464

American (AMR) AF: 0.000131 AC: 2 AN: 15288

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: 4828

European-Finnish (FIN) AF: 0.0000942 AC: 1 AN: 10618

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

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 68046

Other (OTH) AF: 0.000478 AC: 1 AN: 2094

Alfa AF: 0.0000974 Hom.: 0

Bravo AF: 0.0000453

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.0000577 AC: 7

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Apr 19, 2025

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.095
BayesDel_addAF	Benign	-0.51	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	4.3
DANN	Benign	0.16
DEOGEN2	Benign	0.0063	T;T;T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.0047	N
LIST_S2	Benign	0.74	.;T;T
M_CAP	Benign	0.0049	T
MetaRNN	Benign	0.029	T;T;T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	-1.5	N;N;.
PhyloP100		0.34
PrimateAI	Benign	0.28	T
PROVEAN	Benign	0.99	N;N;.
REVEL	Benign	0.012
Sift	Benign	1.0	T;T;.
Sift4G	Benign	0.87	T;T;T
Polyphen		0.0	B;B;.
Vest4		0.12
MVP		0.088
MPC		0.30
ClinPred		0.010	T
GERP RS		1.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.018
gMVP		0.041
Mutation Taster		=98/2	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: rs377391758; hg19: chr7-99219180; COSMIC: COSV99500673; COSMIC: COSV99500673;