rs542266903

Variant names:

• chr1-203798546-C-G
• NM_001395895.1:c.1024C>G

Your query was ambiguous. Multiple possible variants found:

• chr1-203798546-C-G
• chr1-203798546-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001395895.1(ZBED6):​c.1024C>G​(p.Leu342Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000723 in 1,383,808 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/19 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. L342F) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: ZBED6 NM_001395895.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.245

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05640331).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZBED6	NM_001395895.1	c.1024C>G	p.Leu342Val	missense_variant	Exon 1 of 17	ENST00000550078.3	NP_001382824.1
ZC3H11A	NM_001376342.1	c.-1588+2752C>G		intron_variant	Intron 1 of 17	ENST00000367210.3	NP_001363271.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZBED6	ENST00000550078.3	c.1024C>G	p.Leu342Val	missense_variant	Exon 1 of 17	1	NM_001395895.1	ENSP00000447879.1
ZC3H11A	ENST00000367210.3	c.-1588+2752C>G		intron_variant	Intron 1 of 17	1	NM_001376342.1	ENSP00000356179.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.23e-7 AC: 1 AN: 1383808 Hom.: 0 Cov.: 32 AF XY: 0.00000146 AC XY: 1 AN XY: 682848

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.27e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.060
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	8.2
DANN	Benign	0.78
DEOGEN2	Benign	0.0028	T
Eigen	Benign	-0.39
Eigen_PC	Benign	-0.36
FATHMM_MKL	Benign	0.35	N
LIST_S2	Benign	0.39	T
M_CAP	Benign	0.0072	T
MetaRNN	Benign	0.056	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.3	L
PrimateAI	Benign	0.31	T
PROVEAN	Benign	0.14	N
REVEL	Benign	0.012
Sift	Benign	0.50	T
Sift4G	Benign	0.29	T
Vest4		0.027
MutPred		0.19		Loss of stability (P = 0.0799);
MVP		0.061
ClinPred		0.029	T
GERP RS		2.0
Varity_R		0.045
gMVP		0.36

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: chr1-203767674;