19-56221891-C-A

Variant names:

• chr19-56221891-C-A
• rs767840197
• NM_001322064.3:c.1175G>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.1175G>T​(p.Arg392Leu) 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. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R392H) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZSCAN5A NM_001322064.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.187
• 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: 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=0.19477981).

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.1175G>T	p.Arg392Leu	missense	Exon 6 of 6	NP_001308993.1	Q9BUG6-1
	ZSCAN5A	NM_001322065.3		c.1175G>T	p.Arg392Leu	missense	Exon 6 of 6	NP_001308994.1	Q9BUG6-1
	ZSCAN5A	NM_001322066.2		c.1175G>T	p.Arg392Leu	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.1175G>T	p.Arg392Leu	missense	Exon 6 of 6	ENSP00000507065.1	Q9BUG6-1
	ZSCAN5A	ENST00000391713.5	TSL:1	c.1175G>T	p.Arg392Leu	missense	Exon 5 of 5	ENSP00000375593.1	Q9BUG6-1
	ZSCAN5A	ENST00000587340.5	TSL:1	c.1175G>T	p.Arg392Leu	missense	Exon 7 of 7	ENSP00000467631.1	Q9BUG6-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.54
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	8.9
DANN	Benign	0.96
DEOGEN2	Benign	0.022	T
Eigen	Benign	-0.70
Eigen_PC	Benign	-0.91
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.67	T
M_CAP	Benign	0.0025	T
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L
PhyloP100		-0.19
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.047
Sift	Benign	0.098	T
Sift4G	Benign	0.080	T
Polyphen		0.55	P
Vest4		0.11
MutPred		0.59		Loss of methylation at K391 (P = 0.0388)
MVP		0.27
MPC		0.14
ClinPred		0.17	T
GERP RS		-1.4
Varity_R		0.073
gMVP		0.22
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: rs767840197; hg19: chr19-56733260;