chr19-58040492-T-A

Position:

• chr19-58040492-T-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_182572.4(ZSCAN1):​c.413T>A​(p.Phe138Tyr) 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. 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)
• Consequence: ZSCAN1 NM_182572.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.948

Genes affected

ZSCAN1 (HGNC:23712): (zinc finger and SCAN domain containing 1) 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. Predicted to be part of chromatin. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.051380366).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZSCAN1	NM_182572.4	c.413T>A	p.Phe138Tyr	missense_variant	4/6	ENST00000282326.6	NP_872378.3
ZSCAN1	XM_006723149.3	c.533T>A	p.Phe178Tyr	missense_variant	3/5		XP_006723212.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZSCAN1	ENST00000282326.6	c.413T>A	p.Phe138Tyr	missense_variant	4/6	2	NM_182572.4	ENSP00000282326.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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

Aug 28, 2024

The c.413T>A (p.F138Y) alteration is located in exon 4 (coding exon 2) of the ZSCAN1 gene. This alteration results from a T to A substitution at nucleotide position 413, causing the phenylalanine (F) at amino acid position 138 to be replaced by a tyrosine (Y). 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	0.28
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	13
DANN	Benign	0.38
DEOGEN2	Benign	0.099	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.0042	N
LIST_S2	Benign	0.25	T
M_CAP	Benign	0.00099	T
MetaRNN	Benign	0.051	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.34	N
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-0.31	N
REVEL	Benign	0.014
Sift	Benign	1.0	T
Sift4G	Benign	0.81	T
Polyphen		0.39	B
Vest4		0.23
MutPred		0.29		Gain of phosphorylation at F138 (P = 0.003);
MVP		0.14
MPC		0.21
ClinPred		0.10	T
GERP RS		-0.081
Varity_R		0.095
gMVP		0.042

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-58551860;