16-3383109-T-C

Position:

• chr16-3383109-T-C

Variant summary

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

The NM_001284527.2(ZSCAN32):​c.1837A>G​(p.Arg613Gly) 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. 13/21 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: ZSCAN32 NM_001284527.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.184

Genes affected

ZSCAN32 (HGNC:20812): (zinc finger and SCAN domain containing 32) Enables identical protein 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]

ENSG00000285329 (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=0.03749758).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZSCAN32	NM_001284527.2	c.1837A>G	p.Arg613Gly	missense_variant	7/7	ENST00000396852.9	NP_001271456.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZSCAN32	ENST00000396852.9	c.1837A>G	p.Arg613Gly	missense_variant	7/7	1	NM_001284527.2	ENSP00000380061.4
ENSG00000285329	ENST00000575785.2	n.-13+17927T>C		intron_variant		4		ENSP00000477472.1

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

Feb 06, 2023

The c.1201A>G (p.R401G) alteration is located in exon 6 (coding exon 3) of the ZSCAN32 gene. This alteration results from a A to G substitution at nucleotide position 1201, causing the arginine (R) at amino acid position 401 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	Uncertain	0.44
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	16
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0041	T;.;.;T;.
Eigen	Benign	-0.72
Eigen_PC	Benign	-0.67
FATHMM_MKL	Benign	0.000080	N
LIST_S2	Benign	0.33	T;T;T;.;.
M_CAP	Benign	0.0037	T
MetaRNN	Benign	0.037	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.075	N;.;.;N;.
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-0.85	N;.;N;N;N
REVEL	Benign	0.061
Sift	Benign	0.064	T;.;T;T;D
Sift4G	Benign	0.085	T;T;T;T;T
Vest4		0.073
MVP		0.17
MPC		0.021
ClinPred		0.15	T
GERP RS		2.5
Varity_R		0.11
gMVP		0.054

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: chr16-3433109;