chr7-100063958-C-G

Position:

• chr7-100063958-C-G

Variant summary

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

The NM_145914.3(ZSCAN21):​c.763C>G​(p.Gln255Glu) 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: ZSCAN21 NM_145914.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.79

Genes affected

ZSCAN21 (HGNC:13104): (zinc finger and SCAN domain containing 21) Enables DNA-binding transcription activator activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Involved in positive regulation of transcription by RNA polymerase II. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF3 (HGNC:13089): (zinc finger protein 3) Enables identical protein binding activity. Predicted to be involved in negative regulation of transcription by RNA polymerase II. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZSCAN21 (HGNC:):

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=0.060656577).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZSCAN21	NM_145914.3	c.763C>G	p.Gln255Glu	missense_variant	4/4	ENST00000292450.9	NP_666019.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZSCAN21	ENST00000292450.9	c.763C>G	p.Gln255Glu	missense_variant	4/4	1	NM_145914.3	ENSP00000292450.4
ZSCAN21	ENST00000456748.6	c.763C>G	p.Gln255Glu	missense_variant	4/5	5		ENSP00000390960.2
ZSCAN21	ENST00000477297.1	n.689-125C>G		intron_variant		3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

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

Mar 28, 2024

The c.763C>G (p.Q255E) alteration is located in exon 4 (coding exon 3) of the ZSCAN21 gene. This alteration results from a C to G substitution at nucleotide position 763, causing the glutamine (Q) at amino acid position 255 to be replaced by a glutamic acid (E). 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	0.076
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	3.0
DANN	Benign	0.48
DEOGEN2	Benign	0.079	T;T;T
Eigen	Benign	-0.95
Eigen_PC	Benign	-0.98
FATHMM_MKL	Benign	0.25	N
LIST_S2	Benign	0.047	T;T;T
M_CAP	Benign	0.0021	T
MetaRNN	Benign	0.061	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.81	L;.;.
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.11	N;N;.
REVEL	Benign	0.071
Sift	Benign	1.0	T;D;.
Sift4G	Benign	1.0	T;T;T
Polyphen		0.0080	B;.;.
Vest4		0.23
MutPred		0.35		Gain of ubiquitination at K260 (P = 0.0185);Gain of ubiquitination at K260 (P = 0.0185);.;
MVP		0.25
MPC		0.13
ClinPred		0.037	T
GERP RS		3.0
Varity_R		0.036
gMVP		0.066

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: chr7-99661581;