15-43361688-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.1944G>C(p.Glu648Asp) 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 1,461,888 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ZSCAN29 NM_001372080.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0680

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=0.08911428).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZSCAN29	NM_001372080.1	c.1944G>C	p.Glu648Asp	missense_variant	6/6	ENST00000684362.1
ZSCAN29	NM_152455.4	c.1944G>C	p.Glu648Asp	missense_variant	5/5
ZSCAN29	XM_047432187.1	c.1944G>C	p.Glu648Asp	missense_variant	6/6
ZSCAN29	XM_047432188.1	c.966G>C	p.Glu322Asp	missense_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZSCAN29	ENST00000684362.1	c.1944G>C	p.Glu648Asp	missense_variant	6/6		NM_001372080.1	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461888 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727244

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

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

Dec 12, 2023

The c.1944G>C (p.E648D) 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 1944, causing the glutamic acid (E) at amino acid position 648 to be replaced by an aspartic acid (D). 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	0.13
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.71
Cadd	Benign	5.7
Dann	Benign	0.94
DEOGEN2	Benign	0.023	T;T
Eigen	Benign	-0.63
Eigen_PC	Benign	-0.53
FATHMM_MKL	Benign	0.014	N
LIST_S2	Benign	0.52	T;T
M_CAP	Benign	0.0032	T
MetaRNN	Benign	0.089	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.92	L;.
MutationTaster	Benign	1.0	D;N;N;N
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.89	N;N
REVEL	Benign	0.025
Sift	Benign	0.31	T;T
Sift4G	Benign	0.39	T;T
Polyphen		0.0	B;.
Vest4		0.11
MutPred		0.29		Gain of relative solvent accessibility (P = 0.1571);.;
MVP		0.30
MPC		0.084
ClinPred		0.13	T
GERP RS		0.16
Varity_R		0.043
gMVP		0.094

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: chr15-43653886;