chr1-203798240-C-G

Variant names:

• chr1-203798240-C-G
• NM_001395895.1:c.718C>G

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.718C>G​(p.Leu240Val) 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. 15/21 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)
• Consequence: ZBED6 NM_001395895.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.469
• 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=0.08951375).

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.718C>G	p.Leu240Val	missense	Exon 1 of 17	NP_001382824.1	P86452
	ZC3H11A	NM_001376342.1	MANE Select	c.-1588+2446C>G		intron	N/A	NP_001363271.1	O75152
	ZBED6	NM_001174108.2		c.718C>G	p.Leu240Val	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.718C>G	p.Leu240Val	missense	Exon 1 of 17	ENSP00000447879.1	P86452
	ZC3H11A	ENST00000367210.3	TSL:1 MANE Select	c.-1588+2446C>G		intron	N/A	ENSP00000356179.1	O75152
	ZC3H11A	ENST00000332127.8	TSL:1	c.-565+1744C>G		intron	N/A	ENSP00000333253.4	O75152

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

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	0.089
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.00037	T
Eigen	Benign	0.071
Eigen_PC	Benign	0.21
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Benign	0.55	T
M_CAP	Benign	0.0074	T
MetaRNN	Benign	0.090	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.47
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-0.17	N
REVEL	Benign	0.066
Sift	Benign	0.18	T
Sift4G	Pathogenic	0.0	D
Vest4		0.11
MutPred		0.18		Loss of stability (P = 0.0635)
MVP		0.081
ClinPred		0.25	T
GERP RS		5.2
Varity_R		0.15
gMVP		0.25
Mutation Taster		=90/10	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

hg19: chr1-203767368;