19-56221717-G-C

Variant names:

• chr19-56221717-G-C
• rs2033194980
• NM_001322064.3:c.1349C>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_001322064.3(ZSCAN5A):​c.1349C>G​(p.Thr450Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,894 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 Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: ZSCAN5A NM_001322064.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.14
• Publications: 0 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.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.019965619).
• BP6: Variant 19-56221717-G-C is Benign according to our data. Variant chr19-56221717-G-C is described in ClinVar as Likely_benign. ClinVar VariationId is 2246609.Status of the report is criteria_provided_single_submitter, 1 stars.

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.1349C>G	p.Thr450Ser	missense	Exon 6 of 6	NP_001308993.1	Q9BUG6-1
	ZSCAN5A	NM_001322065.3		c.1349C>G	p.Thr450Ser	missense	Exon 6 of 6	NP_001308994.1	Q9BUG6-1
	ZSCAN5A	NM_001322066.2		c.1349C>G	p.Thr450Ser	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.1349C>G	p.Thr450Ser	missense	Exon 6 of 6	ENSP00000507065.1	Q9BUG6-1
	ZSCAN5A	ENST00000391713.5	TSL:1	c.1349C>G	p.Thr450Ser	missense	Exon 5 of 5	ENSP00000375593.1	Q9BUG6-1
	ZSCAN5A	ENST00000587340.5	TSL:1	c.1349C>G	p.Thr450Ser	missense	Exon 7 of 7	ENSP00000467631.1	Q9BUG6-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461894 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 727248

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 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: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

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

European-Non Finnish (NFE) AF: 0.00000360 AC: 4 AN: 1112012

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Likely benign

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	Uncertain	0.43
BayesDel_addAF	Benign	-0.43	T
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.4
DANN	Benign	0.68
DEOGEN2	Benign	0.0094	T
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.015	N
LIST_S2	Benign	0.55	T
M_CAP	Benign	0.0017	T
MetaRNN	Benign	0.020	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	-0.64	N
PhyloP100		-2.1
PrimateAI	Benign	0.43	T
PROVEAN	Benign	0.51	N
REVEL	Benign	0.0070
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.028	B
Vest4		0.012
MutPred		0.25		Gain of phosphorylation at T450 (P = 0.1004)
MVP		0.085
MPC		0.062
ClinPred		0.060	T
GERP RS		-3.7
Varity_R		0.033
gMVP		0.039
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: rs2033194980; hg19: chr19-56733086;