3-101676633-G-A

Variant names:

• chr3-101676633-G-A
• rs1482661124
• NM_014415.4:c.282C>T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_014415.4(ZBTB11):​c.282C>T​(p.His94His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000717 in 1,394,104 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: ZBTB11 NM_014415.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.287
• Publications: 0 publications found

Genes affected

ZBTB11 (HGNC:16740): (zinc finger and BTB domain containing 11) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription, DNA-templated. Located in nucleoplasm. Implicated in autosomal recessive non-syndromic intellectual disability. [provided by Alliance of Genome Resources, Apr 2022]

LOC124906262 (HGNC:):

ZBTB11-AS1 (HGNC:48573): (ZBTB11 antisense RNA 1)

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BP7: Synonymous conserved (PhyloP=0.287 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014415.4. 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
	ZBTB11	NM_014415.4	MANE Select	c.282C>T	p.His94His	synonymous	Exon 1 of 11	NP_055230.2	O95625
	ZBTB11-AS1	NR_024407.1		n.204G>A		non_coding_transcript_exon	Exon 1 of 1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZBTB11	ENST00000312938.5	TSL:1 MANE Select	c.282C>T	p.His94His	synonymous	Exon 1 of 11	ENSP00000326200.4	O95625
	ZBTB11	ENST00000461821.1	TSL:1	c.282C>T	p.His94His	synonymous	Exon 1 of 2	ENSP00000417369.1	C9J2L2
	ZBTB11	ENST00000704111.1		c.282C>T	p.His94His	synonymous	Exon 1 of 10	ENSP00000515702.1	A0A994J7A5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.17e-7 AC: 1 AN: 1394104 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 686164

African (AFR) AF: 0.00 AC: 0 AN: 31256

American (AMR) AF: 0.00 AC: 0 AN: 35460

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22028

East Asian (EAS) AF: 0.00 AC: 0 AN: 38534

South Asian (SAS) AF: 0.00 AC: 0 AN: 77652

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50222

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5474

European-Non Finnish (NFE) AF: 9.29e-7 AC: 1 AN: 1076208

Other (OTH) AF: 0.00 AC: 0 AN: 57270

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	17
DANN	Benign	0.93
PhyloP100		0.29
PromoterAI		-0.0081	Neutral

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: rs1482661124; hg19: chr3-101395477;