1-33491202-A-T

Position:

• chr1-33491202-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001377379.1(ZSCAN20):​c.-11A>T variant causes a 5 prime UTR premature start codon gain 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZSCAN20 NM_001377379.1 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.51

Genes affected

ZSCAN20 (HGNC:13093): (zinc finger and SCAN domain containing 20) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16878304).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZSCAN20	NM_001377376.1	c.944A>T	p.Asp315Val	missense_variant	6/8	ENST00000684572.1	NP_001364305.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZSCAN20	ENST00000684572.1	c.944A>T	p.Asp315Val	missense_variant	6/8		NM_001377376.1	ENSP00000507139.1
ZSCAN20	ENST00000373413.2	c.782A>T	p.Asp261Val	missense_variant	4/4	1		ENSP00000362512.1
ZSCAN20	ENST00000361328.7	c.944A>T	p.Asp315Val	missense_variant	6/8	2		ENSP00000355053.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

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

May 30, 2024

The c.944A>T (p.D315V) alteration is located in exon 6 (coding exon 5) of the ZSCAN20 gene. This alteration results from a A to T substitution at nucleotide position 944, causing the aspartic acid (D) at amino acid position 315 to be replaced by a valine (V). 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	Uncertain	0.39
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	17
DANN	Uncertain	0.98
DEOGEN2	Benign	0.060	T;.
Eigen	Benign	-0.19
Eigen_PC	Benign	-0.22
FATHMM_MKL	Benign	0.58	D
LIST_S2	Benign	0.62	T;T
M_CAP	Benign	0.0060	T
MetaRNN	Benign	0.17	T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Uncertain	2.1	M;.
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-2.3	.;N
REVEL	Benign	0.095
Sift	Benign	0.072	.;T
Sift4G	Benign	0.32	T;T
Polyphen		0.50	P;P
Vest4		0.50
MutPred		0.54		Gain of catalytic residue at D315 (P = 0.001);.;
MVP		0.30
MPC		0.51
ClinPred		0.55	D
GERP RS		2.0
Varity_R		0.10
gMVP		0.33

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: chr1-33956802;