chr19-56221820-C-T

Variant names:

• chr19-56221820-C-T
• rs151298410
• NM_001322064.3:c.1246G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001322064.3(ZSCAN5A):​c.1246G>A​(p.Val416Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000178 in 1,613,884 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00016 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00018 (1 hom.)
• Consequence: ZSCAN5A NM_001322064.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -2.33
• Publications: 2 publications found

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

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0079600215).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001322064.3. 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
	ZSCAN5A	NM_001322064.3	MANE Select	c.1246G>A	p.Val416Ile	missense	Exon 6 of 6	NP_001308993.1	Q9BUG6-1
	ZSCAN5A	NM_001322065.3		c.1246G>A	p.Val416Ile	missense	Exon 6 of 6	NP_001308994.1	Q9BUG6-1
	ZSCAN5A	NM_001322066.2		c.1246G>A	p.Val416Ile	missense	Exon 6 of 6	NP_001308995.1	Q9BUG6-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZSCAN5A	ENST00000683990.1	MANE Select	c.1246G>A	p.Val416Ile	missense	Exon 6 of 6	ENSP00000507065.1	Q9BUG6-1
	ZSCAN5A	ENST00000391713.5	TSL:1	c.1246G>A	p.Val416Ile	missense	Exon 5 of 5	ENSP00000375593.1	Q9BUG6-1
	ZSCAN5A	ENST00000587340.5	TSL:1	c.1246G>A	p.Val416Ile	missense	Exon 7 of 7	ENSP00000467631.1	Q9BUG6-1

Frequencies

GnomAD3 genomes AF: 0.000164 AC: 25 AN: 152158 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000524

Gnomad ASJ AF: 0.00288

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000330 AC: 83 AN: 251326 AF XY: 0.000317

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000174

Gnomad ASJ exome AF: 0.00556

Gnomad EAS exome AF: 0.000381

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000880

Gnomad OTH exome AF: 0.000653

GnomAD4 exome AF: 0.000180 AC: 263 AN: 1461726 Hom.: 1 Cov.: 31 AF XY: 0.000179 AC XY: 130 AN XY: 727148

African (AFR) AF: 0.0000597 AC: 2 AN: 33476

American (AMR) AF: 0.000157 AC: 7 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00498 AC: 130 AN: 26130

East Asian (EAS) AF: 0.000176 AC: 7 AN: 39698

South Asian (SAS) AF: 0.0000580 AC: 5 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53414

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.0000800 AC: 89 AN: 1111884

Other (OTH) AF: 0.000381 AC: 23 AN: 60386

GnomAD4 genome AF: 0.000164 AC: 25 AN: 152158 Hom.: 0 Cov.: 32 AF XY: 0.0000538 AC XY: 4 AN XY: 74332

African (AFR) AF: 0.0000483 AC: 2 AN: 41438

American (AMR) AF: 0.000524 AC: 8 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.00288 AC: 10 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10602

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68036

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.000592 Hom.: 0

Bravo AF: 0.000242

ExAC AF: 0.000313 AC: 38

EpiCase AF: 0.000164

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Benign	-0.61	T
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.046
DANN	Benign	0.90
DEOGEN2	Benign	0.0070	T
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.040	N
LIST_S2	Benign	0.48	T
M_CAP	Benign	0.0011	T
MetaRNN	Benign	0.0080	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.72	N
PhyloP100		-2.3
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.24	N
REVEL	Benign	0.0070
Sift	Benign	0.48	T
Sift4G	Benign	0.81	T
Polyphen		0.0050	B
Vest4		0.093
MVP		0.21
MPC		0.054
ClinPred		0.012	T
GERP RS		-5.5
Varity_R		0.019
gMVP		0.035
Mutation Taster		=100/0	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: rs151298410; hg19: chr19-56733189; COSMIC: COSV54225020; COSMIC: COSV54225020;