chr7-99629250-G-C

Position:

• chr7-99629250-G-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_145115.3(ZSCAN25):​c.865G>C​(p.Val289Leu) 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZSCAN25 NM_145115.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.53

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

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.059826374).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZSCAN25	NM_145115.3	c.865G>C	p.Val289Leu	missense_variant	8/8	ENST00000394152.7	NP_660090.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZSCAN25	ENST00000394152.7	c.865G>C	p.Val289Leu	missense_variant	8/8	5	NM_145115.3	ENSP00000377708	P1

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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 23, 2023

The c.865G>C (p.V289L) alteration is located in exon 8 (coding exon 5) of the ZSCAN25 gene. This alteration results from a G to C substitution at nucleotide position 865, causing the valine (V) at amino acid position 289 to be replaced by a leucine (L). 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	0.19
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	13
DANN	Benign	0.69
DEOGEN2	Benign	0.022	T;T;T
Eigen	Benign	-0.82
Eigen_PC	Benign	-0.76
FATHMM_MKL	Benign	0.46	N
LIST_S2	Benign	0.66	.;T;T
M_CAP	Benign	0.0033	T
MetaRNN	Benign	0.060	T;T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.47	N;N;.
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-0.52	N;N;.
REVEL	Benign	0.039
Sift	Benign	0.58	T;T;.
Sift4G	Benign	0.42	T;T;T
Polyphen		0.018	B;B;.
Vest4		0.032
MutPred		0.23		Gain of helix (P = 0.132);Gain of helix (P = 0.132);.;
MVP		0.18
MPC		0.26
ClinPred		0.10	T
GERP RS		3.9
Varity_R		0.071
gMVP		0.26

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: chr7-99226873;