7-100057731-T-G

Position:

• chr7-100057731-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_145914.3(ZSCAN21):​c.433T>G​(p.Trp145Gly) 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. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZSCAN21 NM_145914.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.65

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]

ZSCAN21 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.26970237).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZSCAN21	NM_145914.3	c.433T>G	p.Trp145Gly	missense_variant	3/4	ENST00000292450.9	NP_666019.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZSCAN21	ENST00000292450.9	c.433T>G	p.Trp145Gly	missense_variant	3/4	1	NM_145914.3	ENSP00000292450.4
ZSCAN21	ENST00000456748.6	c.433T>G	p.Trp145Gly	missense_variant	3/5	5		ENSP00000390960.2
ZSCAN21	ENST00000438937.1	c.433T>G	p.Trp145Gly	missense_variant	4/4	2		ENSP00000404207.1
ZSCAN21	ENST00000477297.1	n.529T>G		non_coding_transcript_exon_variant	2/3	3

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

Dec 07, 2024

The c.433T>G (p.W145G) alteration is located in exon 3 (coding exon 2) of the ZSCAN21 gene. This alteration results from a T to G substitution at nucleotide position 433, causing the tryptophan (W) at amino acid position 145 to be replaced by a glycine (G). 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	0.11
BayesDel_addAF	Benign	-0.038	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	23
DANN	Benign	0.95
DEOGEN2	Uncertain	0.54	D;T;T;T
Eigen	Benign	0.11
Eigen_PC	Benign	0.069
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.20	T;T;T;T
M_CAP	Benign	0.0061	T
MetaRNN	Benign	0.27	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.5	L;.;.;.
PrimateAI	Benign	0.41	T
PROVEAN	Pathogenic	-5.4	D;D;D;.
REVEL	Benign	0.14
Sift	Benign	0.031	D;D;T;.
Sift4G	Benign	0.11	T;D;T;T
Polyphen		0.99	D;.;.;.
Vest4		0.54
MutPred		0.32		Loss of helix (P = 0.0444);Loss of helix (P = 0.0444);Loss of helix (P = 0.0444);.;
MVP		0.35
MPC		0.73
ClinPred		0.96	D
GERP RS		4.2
Varity_R		0.37
gMVP		0.15

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: chr7-99655354;