19-56222051-C-T

Variant names:

• chr19-56222051-C-T
• NM_001322064.3:c.1015G>A

Variant summary

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

The NM_001322064.3(ZSCAN5A):​c.1015G>A​(p.Ala339Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A339V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZSCAN5A NM_001322064.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0100
• 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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.057467222).

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.1015G>A	p.Ala339Thr	missense	Exon 6 of 6	NP_001308993.1	Q9BUG6-1
	ZSCAN5A	NM_001322065.3		c.1015G>A	p.Ala339Thr	missense	Exon 6 of 6	NP_001308994.1	Q9BUG6-1
	ZSCAN5A	NM_001322066.2		c.1015G>A	p.Ala339Thr	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.1015G>A	p.Ala339Thr	missense	Exon 6 of 6	ENSP00000507065.1	Q9BUG6-1
	ZSCAN5A	ENST00000391713.5	TSL:1	c.1015G>A	p.Ala339Thr	missense	Exon 5 of 5	ENSP00000375593.1	Q9BUG6-1
	ZSCAN5A	ENST00000587340.5	TSL:1	c.1015G>A	p.Ala339Thr	missense	Exon 7 of 7	ENSP00000467631.1	Q9BUG6-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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	0.13
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.55
DANN	Benign	0.93
DEOGEN2	Benign	0.0050	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.015	N
LIST_S2	Benign	0.50	T
M_CAP	Benign	0.0011	T
MetaRNN	Benign	0.057	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	2.0	M
PhyloP100		0.010
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.42	N
REVEL	Benign	0.022
Sift	Benign	0.16	T
Sift4G	Benign	0.42	T
Polyphen		0.051	B
Vest4		0.028
MutPred		0.17		Gain of glycosylation at A339 (P = 0.0012)
MVP		0.048
MPC		0.063
ClinPred		0.062	T
GERP RS		-0.21
Varity_R		0.058
gMVP		0.11
Mutation Taster		=98/2	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

hg19: chr19-56733420;