15-43361681-A-G

Position:

• chr15-43361681-A-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.1951T>C​(p.Tyr651His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,886 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: ZSCAN29 NM_001372080.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.40

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=0.083948016).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZSCAN29	NM_001372080.1	c.1951T>C	p.Tyr651His	missense_variant	6/6	ENST00000684362.1
ZSCAN29	NM_152455.4	c.1951T>C	p.Tyr651His	missense_variant	5/5
ZSCAN29	XM_047432187.1	c.1951T>C	p.Tyr651His	missense_variant	6/6
ZSCAN29	XM_047432188.1	c.973T>C	p.Tyr325His	missense_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZSCAN29	ENST00000684362.1	c.1951T>C	p.Tyr651His	missense_variant	6/6		NM_001372080.1	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461886 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727244

Gnomad4 AFR exome AF: 0.0000896

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: 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

Oct 04, 2022

The c.1951T>C (p.Y651H) alteration is located in exon 5 (coding exon 5) of the ZSCAN29 gene. This alteration results from a T to C substitution at nucleotide position 1951, causing the tyrosine (Y) at amino acid position 651 to be replaced by a histidine (H). 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	0.23
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	7.9
DANN	Benign	0.79
DEOGEN2	Benign	0.13	T;T
Eigen	Benign	-0.79
Eigen_PC	Benign	-0.87
FATHMM_MKL	Benign	0.0021	N
LIST_S2	Benign	0.063	T;T
M_CAP	Benign	0.0059	T
MetaRNN	Benign	0.084	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.4	M;.
MutationTaster	Benign	1.0	N;N;N;N
PrimateAI	Benign	0.24	T
PROVEAN	Uncertain	-3.2	D;D
REVEL	Benign	0.080
Sift	Benign	0.047	D;D
Sift4G	Benign	0.13	T;T
Polyphen		0.0	B;.
Vest4		0.15
MutPred		0.47		Loss of phosphorylation at Y651 (P = 0.0298);.;
MVP		0.30
MPC		0.12
ClinPred		0.17	T
GERP RS		0.79
Varity_R		0.11
gMVP		0.17

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: rs867793790; hg19: chr15-43653879;