1-203798607-A-T

Variant names:

• chr1-203798607-A-T
• rs1428605208
• NM_001395895.1:c.1085A>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001395895.1(ZBED6):​c.1085A>T​(p.Asp362Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000145 in 1,383,812 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 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)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: ZBED6 NM_001395895.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.33
• Publications: 0 publications found

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

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=0.11939761).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001395895.1. 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
	ZBED6	NM_001395895.1	MANE Select	c.1085A>T	p.Asp362Val	missense	Exon 1 of 17	NP_001382824.1	P86452
	ZC3H11A	NM_001376342.1	MANE Select	c.-1588+2813A>T		intron	N/A	NP_001363271.1	O75152
	ZBED6	NM_001174108.2		c.1085A>T	p.Asp362Val	missense	Exon 1 of 1	NP_001167579.1	P86452

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZBED6	ENST00000550078.3	TSL:1 MANE Select	c.1085A>T	p.Asp362Val	missense	Exon 1 of 17	ENSP00000447879.1	P86452
	ZC3H11A	ENST00000367210.3	TSL:1 MANE Select	c.-1588+2813A>T		intron	N/A	ENSP00000356179.1	O75152
	ZC3H11A	ENST00000332127.8	TSL:1	c.-565+2111A>T		intron	N/A	ENSP00000333253.4	O75152

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.0000149 AC: 2 AN: 134194 AF XY: 0.0000137

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000818

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000145 AC: 2 AN: 1383812 Hom.: 0 Cov.: 32 AF XY: 0.00000146 AC XY: 1 AN XY: 682846

African (AFR) AF: 0.00 AC: 0 AN: 31594

American (AMR) AF: 0.0000560 AC: 2 AN: 35698

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25182

East Asian (EAS) AF: 0.00 AC: 0 AN: 35734

South Asian (SAS) AF: 0.00 AC: 0 AN: 79236

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33886

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5696

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1078882

Other (OTH) AF: 0.00 AC: 0 AN: 57904

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

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	0.14
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	21
DANN	Benign	0.97
DEOGEN2	Benign	0.0070	T
Eigen	Benign	0.17
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Benign	0.63	T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.6	L
PhyloP100		3.3
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.68	N
REVEL	Benign	0.16
Sift	Benign	0.21	T
Sift4G	Pathogenic	0.0	D
Vest4		0.26
MutPred		0.32		Gain of sheet (P = 0.0507)
MVP		0.48
ClinPred		0.12	T
GERP RS		4.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.3
Varity_R		0.14
gMVP		0.44
Mutation Taster		=92/8	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: rs1428605208; hg19: chr1-203767735;