19-57678455-G-C

Variant names:

• chr19-57678455-G-C
• rs116138022
• NM_152677.4:c.852G>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_152677.4(ZSCAN4):​c.852G>C​(p.Glu284Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00418 in 1,614,124 control chromosomes in the GnomAD database, including 238 homozygotes. 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 Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.022 (133 hom., cov: 32)
  • Exomes 𝑓: 0.0023 (105 hom.)
• Consequence: ZSCAN4 NM_152677.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.32
• Publications: 4 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0027216375).
• BP6: Variant 19-57678455-G-C is Benign according to our data. Variant chr19-57678455-G-C is described in ClinVar as Benign. ClinVar VariationId is 777511.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0736 is higher than 0.05.

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.852G>C	p.Glu284Asp	missense	Exon 5 of 5	NP_689890.1	Q8NAM6
	ZSCAN4	NM_001384833.1		c.852G>C	p.Glu284Asp	missense	Exon 7 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.852G>C	p.Glu284Asp	missense	Exon 5 of 5	ENSP00000321963.4	Q8NAM6

Frequencies

GnomAD3 genomes AF: 0.0218 AC: 3310 AN: 152130 Hom.: 132 Cov.: 32

Gnomad AFR AF: 0.0757

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00825

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.000235

Gnomad OTH AF: 0.0134

GnomAD2 exomes AF: 0.00617 AC: 1550 AN: 251318 AF XY: 0.00452

Gnomad AFR exome AF: 0.0798

Gnomad AMR exome AF: 0.00521

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000475

Gnomad OTH exome AF: 0.00277

GnomAD4 exome AF: 0.00234 AC: 3426 AN: 1461876 Hom.: 105 Cov.: 31 AF XY: 0.00205 AC XY: 1491 AN XY: 727234

African (AFR) AF: 0.0755 AC: 2528 AN: 33480

American (AMR) AF: 0.00570 AC: 255 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.000116 AC: 10 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53406

Middle Eastern (MID) AF: 0.00312 AC: 18 AN: 5768

European-Non Finnish (NFE) AF: 0.000312 AC: 347 AN: 1112010

Other (OTH) AF: 0.00444 AC: 268 AN: 60396

GnomAD4 genome AF: 0.0218 AC: 3323 AN: 152248 Hom.: 133 Cov.: 32 AF XY: 0.0210 AC XY: 1561 AN XY: 74438

African (AFR) AF: 0.0758 AC: 3147 AN: 41534

American (AMR) AF: 0.00830 AC: 127 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5160

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.000235 AC: 16 AN: 68022

Other (OTH) AF: 0.0133 AC: 28 AN: 2110

Alfa AF: 0.00382 Hom.: 13

Bravo AF: 0.0249

TwinsUK AF: 0.000539 AC: 2

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.0747 AC: 329

ESP6500EA AF: 0.000698 AC: 6

ExAC AF: 0.00745 AC: 905

Asia WGS AF: 0.00346 AC: 12 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.000830

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.78	T
BayesDel_noAF	Benign	-0.83
CADD	Benign	8.3
DANN	Benign	0.95
DEOGEN2	Benign	0.014	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.056	N
LIST_S2	Benign	0.35	T
MetaRNN	Benign	0.0027	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	1.3	L
PhyloP100		1.3
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-0.55	N
REVEL	Benign	0.031
Sift	Benign	0.44	T
Sift4G	Benign	0.41	T
Polyphen		0.053	B
Vest4		0.088
MutPred		0.18		Gain of glycosylation at S285 (P = 0.1185)
MVP		0.092
MPC		0.092
ClinPred		0.0036	T
GERP RS		1.6
Varity_R		0.031
gMVP		0.089
Mutation Taster		=100/0	polymorphism (auto)

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: rs116138022; hg19: chr19-58189823;