7-99621557-G-C

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_145115.3(ZSCAN25):​c.572G>C​(p.Arg191Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R191Q) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZSCAN25 NM_145115.3 missense
• Clinical Significance: Not reported in ClinVar
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.074281454).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZSCAN25	NM_145115.3	c.572G>C	p.Arg191Pro	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>C	p.Arg191Pro	missense_variant	Exon 5 of 8	5	NM_145115.3	ENSP00000377708.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	9.0
DANN	Benign	0.78
DEOGEN2	Benign	0.031	T;T;T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.029	N
LIST_S2	Benign	0.77	.;T;T
M_CAP	Benign	0.0074	T
MetaRNN	Benign	0.074	T;T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.20	N;N;.
PhyloP100		0.34
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-1.5	N;N;.
REVEL	Benign	0.013
Sift	Benign	0.060	T;T;.
Sift4G	Benign	0.15	T;T;T
Polyphen		0.046	B;B;.
Vest4		0.20
MutPred		0.18		Gain of glycosylation at R191 (P = 0.0363);Gain of glycosylation at R191 (P = 0.0363);.;
MVP		0.085
MPC		0.44
ClinPred		0.11	T
GERP RS		1.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.28
gMVP		0.11
Mutation Taster		=86/14	polymorphism

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

Other links and lift over

dbSNP: rs377391758; hg19: chr7-99219180;