chr11-130238482-C-T

Variant names:

• chr11-130238482-C-T
• rs1954209188
• NM_001301098.2:c.1229G>A

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001301098.2(ZBTB44):​c.1229G>A​(p.Arg410His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,456,298 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: ZBTB44 NM_001301098.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.54
• Publications: 0 publications found

Genes affected

ZBTB44 (HGNC:25001): (zinc finger and BTB domain containing 44) Predicted to enable DNA binding activity and metal ion binding activity. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.762

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001301098.2. 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
	ZBTB44	NM_001301098.2	MANE Select	c.1229G>A	p.Arg410His	missense	Exon 4 of 8	NP_001288027.1
	ZBTB44	NM_001370219.1		c.1229G>A	p.Arg410His	missense	Exon 4 of 6	NP_001357148.1	H0YEM9
	ZBTB44	NM_001370220.1		c.1175G>A	p.Arg392His	missense	Exon 4 of 6	NP_001357149.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZBTB44	ENST00000357899.9	TSL:1 MANE Select	c.1229G>A	p.Arg410His	missense	Exon 4 of 8	ENSP00000350574.4
	ZBTB44	ENST00000530205.5	TSL:1	c.1229G>A	p.Arg410His	missense	Exon 3 of 6	ENSP00000434177.1	Q8NCP5-2
	ZBTB44	ENST00000525842.5	TSL:1	c.1229G>A	p.Arg410His	missense	Exon 4 of 6	ENSP00000433457.1	Q8NCP5-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1456298 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 723738

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 33412

American (AMR) AF: 0.00 AC: 0 AN: 43972

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25940

East Asian (EAS) AF: 0.00 AC: 0 AN: 39590

South Asian (SAS) AF: 0.00 AC: 0 AN: 84814

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53218

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5758

European-Non Finnish (NFE) AF: 9.01e-7 AC: 1 AN: 1109368

Other (OTH) AF: 0.00 AC: 0 AN: 60226

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

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	0.94
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Uncertain	0.020
CADD	Pathogenic	30
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.011	T
Eigen	Uncertain	0.43
Eigen_PC	Uncertain	0.57
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.063	D
MetaRNN	Pathogenic	0.76	D
MetaSVM	Benign	-0.88	T
MutationAssessor	Benign	0.55	N
PhyloP100		7.5
PrimateAI	Pathogenic	0.95	D
PROVEAN	Benign	-1.4	N
REVEL	Uncertain	0.42
Sift	Benign	0.53	T
Sift4G	Uncertain	0.019	D
Polyphen		1.0	D
Vest4		0.53
MutPred		0.70		Loss of MoRF binding (P = 0.0144)
MVP		0.47
MPC		1.4
ClinPred		0.96	D
GERP RS		6.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
gMVP		0.64
Mutation Taster		=20/80	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

Other links and lift over

dbSNP: rs1954209188; hg19: chr11-130108377;