19-56221585-G-A

Variant names:

• chr19-56221585-G-A
• rs199652968
• NM_001322064.3:c.1481C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001322064.3(ZSCAN5A):​c.1481C>T​(p.Thr494Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000357 in 1,597,064 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000037 (0 hom.)
• Consequence: ZSCAN5A NM_001322064.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.576
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.089787126).

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.1481C>T	p.Thr494Ile	missense	Exon 6 of 6	NP_001308993.1	Q9BUG6-1
	ZSCAN5A	NM_001322065.3		c.1481C>T	p.Thr494Ile	missense	Exon 6 of 6	NP_001308994.1	Q9BUG6-1
	ZSCAN5A	NM_001322066.2		c.1481C>T	p.Thr494Ile	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.1481C>T	p.Thr494Ile	missense	Exon 6 of 6	ENSP00000507065.1	Q9BUG6-1
	ZSCAN5A	ENST00000391713.5	TSL:1	c.1481C>T	p.Thr494Ile	missense	Exon 5 of 5	ENSP00000375593.1	Q9BUG6-1
	ZSCAN5A	ENST00000587340.5	TSL:1	c.1481C>T	p.Thr494Ile	missense	Exon 7 of 7	ENSP00000467631.1	Q9BUG6-1

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152242 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000377 AC: 9 AN: 238726 AF XY: 0.0000309

Gnomad AFR exome AF: 0.0000625

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000730

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000374 AC: 54 AN: 1444822 Hom.: 0 Cov.: 30 AF XY: 0.0000376 AC XY: 27 AN XY: 717852

African (AFR) AF: 0.0000309 AC: 1 AN: 32378

American (AMR) AF: 0.00 AC: 0 AN: 41150

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25066

East Asian (EAS) AF: 0.00 AC: 0 AN: 39520

South Asian (SAS) AF: 0.00 AC: 0 AN: 84214

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53058

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5632

European-Non Finnish (NFE) AF: 0.0000471 AC: 52 AN: 1104274

Other (OTH) AF: 0.0000168 AC: 1 AN: 59530

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152242 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74370

African (AFR) AF: 0.00 AC: 0 AN: 41458

American (AMR) AF: 0.00 AC: 0 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5202

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

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

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68050

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

Alfa AF: 0.0000409 Hom.: 0

Bravo AF: 0.0000227

ExAC AF: 0.0000247 AC: 3

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	0.21
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	8.3
DANN	Uncertain	0.98
DEOGEN2	Benign	0.021	T
Eigen	Benign	-0.86
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.017	N
LIST_S2	Benign	0.37	T
M_CAP	Benign	0.00081	T
MetaRNN	Benign	0.090	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.5	L
PhyloP100		0.58
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.066
Sift	Benign	0.047	D
Sift4G	Benign	0.31	T
Polyphen		0.93	P
Vest4		0.075
MutPred		0.24		Loss of glycosylation at T494 (P = 0.0579)
MVP		0.18
MPC		0.25
ClinPred		0.061	T
GERP RS		-2.4
Varity_R		0.039
gMVP		0.11
Mutation Taster		=87/13	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: rs199652968; hg19: chr19-56732954;