16-3382884-G-C

Variant names:

• chr16-3382884-G-C
• rs556687010
• NM_001284527.2:c.2062C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001284527.2(ZSCAN32):​c.2062C>G​(p.Leu688Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000631 in 1,584,754 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L688F) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000056 (0 hom.)
• Consequence: ZSCAN32 NM_001284527.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.663
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.058947563).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001284527.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZSCAN32	NM_001284527.2	MANE Select	c.2062C>G	p.Leu688Val	missense	Exon 7 of 7	NP_001271456.1	Q9NX65-1
	ZSCAN32	NM_001324346.2		c.1843C>G	p.Leu615Val	missense	Exon 5 of 5	NP_001311275.1
	ZSCAN32	NM_001324343.2		c.1663C>G	p.Leu555Val	missense	Exon 6 of 6	NP_001311272.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZSCAN32	ENST00000396852.9	TSL:1 MANE Select	c.2062C>G	p.Leu688Val	missense	Exon 7 of 7	ENSP00000380061.4	Q9NX65-1
	ZSCAN32	ENST00000304926.7	TSL:1	c.1426C>G	p.Leu476Val	missense	Exon 6 of 6	ENSP00000302502.3	Q9NX65-2
	ENSG00000285329	ENST00000575785.2	TSL:4	n.-13+17702G>C		intron	N/A	ENSP00000477472.1	V9GZ69

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152208 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000428 AC: 1 AN: 233718 AF XY: 0.00000791

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000558 AC: 8 AN: 1432428 Hom.: 0 Cov.: 31 AF XY: 0.00000705 AC XY: 5 AN XY: 709516

African (AFR) AF: 0.0000932 AC: 3 AN: 32188

American (AMR) AF: 0.00 AC: 0 AN: 40316

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24512

East Asian (EAS) AF: 0.00 AC: 0 AN: 39262

South Asian (SAS) AF: 0.0000597 AC: 5 AN: 83710

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52654

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5624

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1095266

Other (OTH) AF: 0.00 AC: 0 AN: 58896

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152326 Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1 AN XY: 74486

African (AFR) AF: 0.0000241 AC: 1 AN: 41568

American (AMR) AF: 0.00 AC: 0 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68034

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.0000165 AC: 2

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	13
DANN	Benign	0.94
DEOGEN2	Benign	0.0079	T
Eigen	Benign	-0.74
Eigen_PC	Benign	-0.90
FATHMM_MKL	Benign	0.000050	N
LIST_S2	Benign	0.15	T
M_CAP	Benign	0.0020	T
MetaRNN	Benign	0.059	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.040	N
PhyloP100		0.66
PrimateAI	Benign	0.21	T
PROVEAN	Benign	-0.79	N
REVEL	Benign	0.061
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.17	T
Vest4		0.060
MVP		0.11
MPC		0.019
ClinPred		0.084	T
GERP RS		0.40
Varity_R		0.072
gMVP		0.012
Mutation Taster		=99/1	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

dbSNP: rs556687010; hg19: chr16-3432884;