NM_001322064.3:c.958G>A

Variant names:

• chr19-56222108-C-T
• NM_001322064.3:c.958G>A

Variant summary

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

The NM_001322064.3(ZSCAN5A):​c.958G>A​(p.Gly320Ser) 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: ZSCAN5A NM_001322064.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -2.07

Genes affected

ZSCAN5A (HGNC:23710): (zinc finger and SCAN domain containing 5A) 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=0.09114486).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZSCAN5A	NM_001322064.3	c.958G>A	p.Gly320Ser	missense_variant	Exon 6 of 6	ENST00000683990.1	NP_001308993.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZSCAN5A	ENST00000683990.1	c.958G>A	p.Gly320Ser	missense_variant	Exon 6 of 6		NM_001322064.3	ENSP00000507065.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 11, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.958G>A (p.G320S) alteration is located in exon 5 (coding exon 4) of the ZSCAN5A gene. This alteration results from a G to A substitution at nucleotide position 958, causing the glycine (G) at amino acid position 320 to be replaced by a serine (S). 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	0.14
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	8.9
DANN	Benign	0.92
DEOGEN2	Benign	0.014	T;.;T;T;T
Eigen	Benign	-0.65
Eigen_PC	Benign	-0.95
FATHMM_MKL	Benign	0.016	N
LIST_S2	Benign	0.70	.;T;T;T;T
M_CAP	Benign	0.0022	T
MetaRNN	Benign	0.091	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.5	M;.;M;.;.
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-0.77	N;.;.;.;.
REVEL	Benign	0.046
Sift	Benign	0.10	T;.;.;.;.
Sift4G	Benign	0.43	T;T;T;T;D
Polyphen		1.0	D;.;D;.;.
Vest4		0.085
MutPred		0.26		Gain of phosphorylation at G320 (P = 0.0111);.;Gain of phosphorylation at G320 (P = 0.0111);.;.;
MVP		0.19
MPC		0.39
ClinPred		0.26	T
GERP RS		-0.074
Varity_R		0.059
gMVP		0.12

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: chr19-56733477;