6-28232816-A-G

Position:

• chr6-28232816-A-G

Variant summary

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

The NM_006299.5(ZSCAN9):​c.823A>G​(p.Ile275Val) 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. 14/21 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: ZSCAN9 NM_006299.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.181

Genes affected

ZSCAN9 (HGNC:12984): (zinc finger and SCAN domain containing 9) 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=0.10559541).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZSCAN9	NM_006299.5	c.823A>G	p.Ile275Val	missense_variant	4/4	ENST00000252207.10	NP_006290.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZSCAN9	ENST00000252207.10	c.823A>G	p.Ile275Val	missense_variant	4/4	1	NM_006299.5	ENSP00000252207	P2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000795 AC: 2 AN: 251422 Hom.: 0 AF XY: 0.00000736 AC XY: 1 AN XY: 135892

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000109

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

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

Feb 05, 2024

The c.976A>G (p.I326V) alteration is located in exon 5 (coding exon 4) of the ZSCAN9 gene. This alteration results from a A to G substitution at nucleotide position 976, causing the isoleucine (I) at amino acid position 326 to be replaced by a valine (V). 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	Uncertain	0.38
BayesDel_addAF	Benign	-0.47	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	11
DANN	Benign	0.94
DEOGEN2	Benign	0.027	.;T;T;.
Eigen	Benign	-0.68
Eigen_PC	Benign	-0.67
FATHMM_MKL	Benign	0.34	N
LIST_S2	Benign	0.13	T;.;T;T
M_CAP	Benign	0.0041	T
MetaRNN	Benign	0.11	T;T;T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	-0.17	.;N;N;.
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-0.38	N;N;N;N
REVEL	Benign	0.051
Sift	Benign	0.19	T;T;T;T
Sift4G	Benign	0.16	T;T;T;T
Polyphen		0.0010	.;B;B;.
Vest4		0.089
MutPred		0.71		.;Loss of stability (P = 0.1184);Loss of stability (P = 0.1184);.;
MVP		0.076
MPC		0.095
ClinPred		0.035	T
GERP RS		3.0
Varity_R		0.027
gMVP		0.028

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: rs771195135; hg19: chr6-28200594;