16-3383306-T-A

Variant names:

• chr16-3383306-T-A
• rs2031482155
• NM_001284527.2:c.1640A>T

Variant summary

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

The NM_001284527.2(ZSCAN32):​c.1640A>T​(p.Lys547Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,892 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ZSCAN32 NM_001284527.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0710

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 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=0.30106443).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZSCAN32	NM_001284527.2	c.1640A>T	p.Lys547Met	missense_variant	Exon 7 of 7	ENST00000396852.9	NP_001271456.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZSCAN32	ENST00000396852.9	c.1640A>T	p.Lys547Met	missense_variant	Exon 7 of 7	1	NM_001284527.2	ENSP00000380061.4
ENSG00000285329	ENST00000575785.2	n.-13+18124T>A		intron_variant	Intron 1 of 4	4		ENSP00000477472.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461892 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727248

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 07, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1004A>T (p.K335M) alteration is located in exon 6 (coding exon 3) of the ZSCAN32 gene. This alteration results from a A to T substitution at nucleotide position 1004, causing the lysine (K) at amino acid position 335 to be replaced by a methionine (M). 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	Pathogenic	0.85
BayesDel_addAF	Benign	-0.082	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.38	T;.;.;T;.
Eigen	Uncertain	0.30
Eigen_PC	Benign	0.17
FATHMM_MKL	Benign	0.0025	N
LIST_S2	Benign	0.63	T;T;T;.;.
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.30	T;T;T;T;T
MetaSVM	Benign	-0.58	T
MutationAssessor	Uncertain	2.8	M;.;.;M;.
PrimateAI	Benign	0.46	T
PROVEAN	Pathogenic	-5.5	D;.;D;D;D
REVEL	Benign	0.25
Sift	Pathogenic	0.0	D;.;D;D;D
Sift4G	Pathogenic	0.0	D;D;D;D;D
Vest4		0.34
MVP		0.44
MPC		0.11
ClinPred		0.98	D
GERP RS		3.8
Varity_R		0.52
gMVP		0.038

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

LitVar

Other links and lift over

dbSNP: rs2031482155; hg19: chr16-3433306;