chr1-203798792-C-T

Position:

• chr1-203798792-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001395895.1(ZBED6):​c.1270C>T​(p.Pro424Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZBED6 NM_001395895.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.28

Genes affected

ZBED6 (HGNC:33273): (zinc finger BED-type containing 6) The protein encoded by this transposon-derived intronless gene is a transcriptional repressor that binds to the consensus sequence 5'-GCTCGC-3'. The encoded protein has been shown to repress IGF2 transcription. This gene is located within the first intron of the ZC3H11A gene. [provided by RefSeq, Jul 2016]

ZC3H11A (HGNC:29093): (zinc finger CCCH-type containing 11A) Enables RNA binding activity. Involved in poly(A)+ mRNA export from nucleus. Colocalizes with transcription export complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.815

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZBED6	NM_001395895.1	c.1270C>T	p.Pro424Ser	missense_variant	1/17	ENST00000550078.3
ZC3H11A	NM_001376342.1	c.-1587-2783C>T		intron_variant		ENST00000367210.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZBED6	ENST00000550078.3	c.1270C>T	p.Pro424Ser	missense_variant	1/17	1	NM_001395895.1	P1
ZC3H11A	ENST00000367210.3	c.-1587-2783C>T		intron_variant		1	NM_001376342.1	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 14, 2023

The c.1270C>T (p.P424S) alteration is located in exon 1 (coding exon 1) of the ZBED6 gene. This alteration results from a C to T substitution at nucleotide position 1270, causing the proline (P) at amino acid position 424 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.33
BayesDel_addAF	Pathogenic	0.41	D
BayesDel_noAF	Pathogenic	0.36
CADD	Uncertain	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.088	T
Eigen	Uncertain	0.38
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.59	T
M_CAP	Benign	0.032	D
MetaRNN	Pathogenic	0.81	D
MetaSVM	Benign	-0.58	T
MutationAssessor	Benign	2.0	M
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Uncertain	0.56	T
PROVEAN	Pathogenic	-7.0	D
REVEL	Uncertain	0.36
Sift	Uncertain	0.0030	D
Sift4G	Pathogenic	0.0	D
Vest4		0.70
MutPred		0.80		Loss of catalytic residue at M422 (P = 0.0253);
MVP		0.17
ClinPred		0.96	D
GERP RS		4.6
Varity_R		0.59
gMVP		0.79

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-203767920;