19-56190954-C-T

Variant names:

• chr19-56190954-C-T
• rs4801296
• NM_001080456.5:c.622G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001080456.5(ZSCAN5B):​c.622G>A​(p.Val208Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.386 in 1,613,572 control chromosomes in the GnomAD database, including 124,877 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.47 (18246 hom., cov: 31)
  • Exomes 𝑓: 0.38 (106631 hom.)
• Consequence: ZSCAN5B NM_001080456.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.74
• Publications: 22 publications found

Genes affected

ZSCAN5B (HGNC:34246): (zinc finger and SCAN domain containing 5B) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific 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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=2.675906E-6).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.677 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001080456.5. 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
	ZSCAN5B	NM_001080456.5	MANE Select	c.622G>A	p.Val208Ile	missense	Exon 4 of 5	NP_001073925.2	A6NJL1
	ZSCAN5B	NM_001385638.1		c.622G>A	p.Val208Ile	missense	Exon 4 of 5	NP_001372567.1	A6NJL1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZSCAN5B	ENST00000586855.7	TSL:5 MANE Select	c.622G>A	p.Val208Ile	missense	Exon 4 of 5	ENSP00000466072.2	A6NJL1

Frequencies

GnomAD3 genomes AF: 0.468 AC: 70967 AN: 151718 Hom.: 18211 Cov.: 31

Gnomad AFR AF: 0.684

Gnomad AMI AF: 0.367

Gnomad AMR AF: 0.447

Gnomad ASJ AF: 0.455

Gnomad EAS AF: 0.401

Gnomad SAS AF: 0.389

Gnomad FIN AF: 0.375

Gnomad MID AF: 0.595

Gnomad NFE AF: 0.368

Gnomad OTH AF: 0.455

GnomAD2 exomes AF: 0.407 AC: 102351 AN: 251326 AF XY: 0.400

Gnomad AFR exome AF: 0.689

Gnomad AMR exome AF: 0.439

Gnomad ASJ exome AF: 0.443

Gnomad EAS exome AF: 0.410

Gnomad FIN exome AF: 0.364

Gnomad NFE exome AF: 0.369

Gnomad OTH exome AF: 0.412

GnomAD4 exome AF: 0.377 AC: 551390 AN: 1461736 Hom.: 106631 Cov.: 60 AF XY: 0.377 AC XY: 274210 AN XY: 727178

African (AFR) AF: 0.698 AC: 23359 AN: 33472

American (AMR) AF: 0.442 AC: 19726 AN: 44672

Ashkenazi Jewish (ASJ) AF: 0.446 AC: 11644 AN: 26124

East Asian (EAS) AF: 0.390 AC: 15468 AN: 39698

South Asian (SAS) AF: 0.382 AC: 32973 AN: 86252

European-Finnish (FIN) AF: 0.356 AC: 19029 AN: 53418

Middle Eastern (MID) AF: 0.538 AC: 3103 AN: 5764

European-Non Finnish (NFE) AF: 0.361 AC: 401961 AN: 1111946

Other (OTH) AF: 0.400 AC: 24127 AN: 60390

GnomAD4 genome AF: 0.468 AC: 71060 AN: 151836 Hom.: 18246 Cov.: 31 AF XY: 0.467 AC XY: 34642 AN XY: 74202

African (AFR) AF: 0.684 AC: 28298 AN: 41362

American (AMR) AF: 0.448 AC: 6830 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.455 AC: 1577 AN: 3468

East Asian (EAS) AF: 0.401 AC: 2062 AN: 5148

South Asian (SAS) AF: 0.389 AC: 1875 AN: 4818

European-Finnish (FIN) AF: 0.375 AC: 3951 AN: 10540

Middle Eastern (MID) AF: 0.612 AC: 180 AN: 294

European-Non Finnish (NFE) AF: 0.368 AC: 25002 AN: 67930

Other (OTH) AF: 0.451 AC: 950 AN: 2108

Alfa AF: 0.408 Hom.: 29414

Bravo AF: 0.482

TwinsUK AF: 0.365 AC: 1353

ALSPAC AF: 0.360 AC: 1386

ESP6500AA AF: 0.683 AC: 3010

ESP6500EA AF: 0.366 AC: 3149

ExAC AF: 0.407 AC: 49420

Asia WGS AF: 0.410 AC: 1427 AN: 3478

EpiCase AF: 0.388

EpiControl AF: 0.385

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.88	T
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.27
DANN	Benign	0.64
DEOGEN2	Benign	0.0036	T
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.00035	N
LIST_S2	Benign	0.34	T
MetaRNN	Benign	0.0000027	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.29	N
PhyloP100		-1.7
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.33	N
REVEL	Benign	0.016
Sift	Benign	0.19	T
Sift4G	Benign	0.21	T
Polyphen		0.0	B
Vest4		0.0080
MPC		0.013
ClinPred		0.0013	T
GERP RS		-2.6
Varity_R		0.026
gMVP		0.040
Mutation Taster		=84/16	polymorphism

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

Other links and lift over

dbSNP: rs4801296; hg19: chr19-56702323; COSMIC: COSV62839497; COSMIC: COSV62839497;