19-57676216-C-G

Variant names:

• chr19-57676216-C-G
• rs749904831
• NM_152677.4:c.71C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_152677.4(ZSCAN4):​c.71C>G​(p.Ala24Gly) 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. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A24V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZSCAN4 NM_152677.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.126
• Publications: 0 publications found

Genes affected

ZSCAN4 (HGNC:23709): (zinc finger and SCAN domain containing 4) The ZSCAN4 gene encodes a protein involved in telomere maintenance and with a key role in the critical feature of mouse embryonic stem (ES) cells, namely, defying cellular senescence and maintaining normal karyotype for many cell divisions in culture (Zalzman et al., 2010 [PubMed 20336070]).[supplied by OMIM, May 2010]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.050260365).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152677.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZSCAN4	NM_152677.4	MANE Select	c.71C>G	p.Ala24Gly	missense	Exon 3 of 5	NP_689890.1	Q8NAM6
	ZSCAN4	NM_001384833.1		c.71C>G	p.Ala24Gly	missense	Exon 5 of 7	NP_001371762.1	Q8NAM6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZSCAN4	ENST00000318203.9	TSL:2 MANE Select	c.71C>G	p.Ala24Gly	missense	Exon 3 of 5	ENSP00000321963.4	Q8NAM6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.79
CADD	Benign	3.9
DANN	Benign	0.85
DEOGEN2	Benign	0.011	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.0054	N
LIST_S2	Benign	0.19	T
M_CAP	Benign	0.0023	T
MetaRNN	Benign	0.050	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.69	N
PhyloP100		-0.13
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.58	N
REVEL	Benign	0.0080
Sift	Benign	0.067	T
Sift4G	Benign	0.26	T
Polyphen		0.010	B
Vest4		0.032
MutPred		0.15		Loss of loop (P = 0.0288)
MVP		0.10
MPC		0.080
ClinPred		0.042	T
GERP RS		1.7
Varity_R		0.050
gMVP		0.052
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs749904831; hg19: chr19-58187584;