rs768246770

Variant names:

• chr19-56190005-C-A
• rs768246770
• NM_001080456.5:c.1310G>T

Your query was ambiguous. Multiple possible variants found:

• chr19-56190005-C-A
• chr19-56190005-C-G
• chr19-56190005-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001080456.5(ZSCAN5B):​c.1310G>T​(p.Arg437Met) 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. 12/21 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. R437K) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZSCAN5B NM_001080456.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.535

Genes affected

ZSCAN5B (HGNC:34246): (zinc finger and SCAN domain containing 5B) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific 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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14442486).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZSCAN5B	NM_001080456.5	c.1310G>T	p.Arg437Met	missense_variant	Exon 5 of 5	ENST00000586855.7	NP_001073925.2
ZSCAN5B	NM_001385638.1	c.1310G>T	p.Arg437Met	missense_variant	Exon 5 of 5		NP_001372567.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZSCAN5B	ENST00000586855.7	c.1310G>T	p.Arg437Met	missense_variant	Exon 5 of 5	5	NM_001080456.5	ENSP00000466072.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.96
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	14
DANN	Benign	0.94
DEOGEN2	Benign	0.14	T;T
Eigen	Benign	-0.78
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.36	.;T
M_CAP	Benign	0.0016	T
MetaRNN	Benign	0.14	T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Uncertain	2.5	M;M
PrimateAI	Benign	0.39	T
PROVEAN	Uncertain	-3.5	.;D
REVEL	Benign	0.054
Sift	Uncertain	0.0010	.;D
Sift4G	Pathogenic	0.0010	D;D
Polyphen		0.97	D;D
Vest4		0.22
MutPred		0.47		Loss of MoRF binding (P = 0.0224);Loss of MoRF binding (P = 0.0224);
MVP		0.099
MPC		0.070
ClinPred		0.77	D
GERP RS		-4.4
Varity_R		0.089
gMVP		0.21

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

Publications

LitVar

Other links and lift over

dbSNP: rs768246770; hg19: chr19-56701374;