NM_145914.3:c.431T>G

Variant names:

• chr7-100057729-T-G
• NM_145914.3:c.431T>G

Variant summary

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

The NM_145914.3(ZSCAN21):​c.431T>G​(p.Val144Gly) 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. 15/22 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: -0.253
• Publications: 0 publications found

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]

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=0.097762644).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZSCAN21	NM_145914.3	c.431T>G	p.Val144Gly	missense_variant	Exon 3 of 4	ENST00000292450.9	NP_666019.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZSCAN21	ENST00000292450.9	c.431T>G	p.Val144Gly	missense_variant	Exon 3 of 4	1	NM_145914.3	ENSP00000292450.4
ZSCAN21	ENST00000456748.6	c.431T>G	p.Val144Gly	missense_variant	Exon 3 of 5	5		ENSP00000390960.2
ZSCAN21	ENST00000438937.1	c.431T>G	p.Val144Gly	missense_variant	Exon 4 of 4	2		ENSP00000404207.1
ZSCAN21	ENST00000477297.1	n.527T>G		non_coding_transcript_exon_variant	Exon 2 of 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

May 25, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.431T>G (p.V144G) 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 431, causing the valine (V) at amino acid position 144 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	-0.27	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	5.8
DANN	Benign	0.84
DEOGEN2	Uncertain	0.49	T;T;T;T
Eigen	Benign	-0.86
Eigen_PC	Benign	-0.96
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.21	T;T;T;T
M_CAP	Benign	0.0042	T
MetaRNN	Benign	0.098	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.2	L;.;.;.
PhyloP100		-0.25
PrimateAI	Benign	0.26	T
PROVEAN	Uncertain	-3.7	D;D;D;.
REVEL	Benign	0.040
Sift	Benign	0.26	T;D;T;.
Sift4G	Benign	0.33	T;D;T;T
Polyphen		0.020	B;.;.;.
Vest4		0.11
MutPred		0.22		Loss of stability (P = 0.0567);Loss of stability (P = 0.0567);Loss of stability (P = 0.0567);.;
MVP		0.33
MPC		0.15
ClinPred		0.17	T
GERP RS		-0.96
Varity_R		0.12
gMVP		0.12
Mutation Taster		=94/6	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

hg19: chr7-99655352;