1-203798787-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001395895.1(ZBED6):c.1265T>C(p.Met422Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign 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: 4.33

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.27998608).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZBED6	NM_001395895.1	c.1265T>C	p.Met422Thr	missense_variant	1/17	ENST00000550078.3
ZC3H11A	NM_001376342.1	c.-1587-2788T>C		intron_variant		ENST00000367210.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZBED6	ENST00000550078.3	c.1265T>C	p.Met422Thr	missense_variant	1/17	1	NM_001395895.1	P1
ZC3H11A	ENST00000367210.3	c.-1587-2788T>C		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

Feb 21, 2024

The c.1265T>C (p.M422T) alteration is located in exon 1 (coding exon 1) of the ZBED6 gene. This alteration results from a T to C substitution at nucleotide position 1265, causing the methionine (M) at amino acid position 422 to be replaced by a threonine (T). 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	0.29
BayesDel_addAF	Uncertain	0.035	T
BayesDel_noAF	Benign	-0.19
Cadd	Benign	21
Dann	Benign	0.96
DEOGEN2	Benign	0.014	T
Eigen	Benign	0.18
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.42	T
M_CAP	Benign	0.0087	T
MetaRNN	Benign	0.28	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	L
MutationTaster	Benign	1.0	D;D;D;N
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.12
Sift	Benign	0.033	D
Sift4G	Uncertain	0.015	D
Vest4		0.53
MutPred		0.52		Loss of stability (P = 0.062);
MVP		0.26
ClinPred		0.45	T
GERP RS		4.5
Varity_R		0.27
gMVP		0.45

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: chr1-203767915;