chr15-43361336-C-G

Position:

• chr15-43361336-C-G

Variant summary

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

The NM_001372080.1(ZSCAN29):​c.2296G>C​(p.Glu766Gln) 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: ZSCAN29 NM_001372080.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.202

Genes affected

ZSCAN29 (HGNC:26673): (zinc finger and SCAN domain containing 29) Enables sequence-specific double-stranded 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=0.12879878).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZSCAN29	NM_001372080.1	c.2296G>C	p.Glu766Gln	missense_variant	6/6	ENST00000684362.1
ZSCAN29	NM_152455.4	c.2296G>C	p.Glu766Gln	missense_variant	5/5
ZSCAN29	XM_047432187.1	c.2296G>C	p.Glu766Gln	missense_variant	6/6
ZSCAN29	XM_047432188.1	c.1318G>C	p.Glu440Gln	missense_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZSCAN29	ENST00000684362.1	c.2296G>C	p.Glu766Gln	missense_variant	6/6		NM_001372080.1	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000756

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

Dec 14, 2023

The c.2296G>C (p.E766Q) alteration is located in exon 5 (coding exon 5) of the ZSCAN29 gene. This alteration results from a G to C substitution at nucleotide position 2296, causing the glutamic acid (E) at amino acid position 766 to be replaced by a glutamine (Q). 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	0.31
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.022	T;T
Eigen	Benign	-0.19
Eigen_PC	Benign	-0.071
FATHMM_MKL	Benign	0.0053	N
LIST_S2	Benign	0.61	T;T
M_CAP	Benign	0.0025	T
MetaRNN	Benign	0.13	T;T
MetaSVM	Benign	-0.82	T
MutationAssessor	Benign	0.54	N;.
MutationTaster	Benign	0.60	D;D;D;N
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-2.0	N;N
REVEL	Benign	0.11
Sift	Uncertain	0.014	D;T
Sift4G	Uncertain	0.049	D;D
Polyphen		0.29	B;.
Vest4		0.27
MutPred		0.63		Loss of helix (P = 0.1706);.;
MVP		0.29
MPC		0.18
ClinPred		0.39	T
GERP RS		5.2
Varity_R		0.20
gMVP		0.23

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs2043976862; hg19: chr15-43653534;