3-101676880-C-G

Variant names:

• chr3-101676880-C-G
• rs1937184829
• NM_014415.4:c.35G>C

Variant summary

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

The NM_014415.4(ZBTB11):​c.35G>C​(p.Arg12Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZBTB11 NM_014415.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.23
• 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.35G>C	p.Arg12Pro	missense	Exon 1 of 11	NP_055230.2	O95625
	ZBTB11-AS1	NR_024407.1		n.451C>G		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.35G>C	p.Arg12Pro	missense	Exon 1 of 11	ENSP00000326200.4	O95625
	ZBTB11	ENST00000461821.1	TSL:1	c.35G>C	p.Arg12Pro	missense	Exon 1 of 2	ENSP00000417369.1	C9J2L2
	ZBTB11	ENST00000704111.1		c.35G>C	p.Arg12Pro	missense	Exon 1 of 10	ENSP00000515702.1	A0A994J7A5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

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	Pathogenic	0.98
PhyloP100		7.2
PromoterAI		-0.079	Neutral
Varity_R		0.62
gMVP		0.91
Mutation Taster		=40/60	disease causing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs1937184829; hg19: chr3-101395724;