NM_001301098.2:c.684T>G

Variant names:

• chr11-130261190-A-C
• NM_001301098.2:c.684T>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001301098.2(ZBTB44):​c.684T>G​(p.Phe228Leu) 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. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZBTB44 NM_001301098.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.30
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19922352).

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.684T>G	p.Phe228Leu	missense	Exon 2 of 8	NP_001288027.1
	ZBTB44	NM_001370219.1		c.684T>G	p.Phe228Leu	missense	Exon 2 of 6	NP_001357148.1	H0YEM9
	ZBTB44	NM_001370220.1		c.684T>G	p.Phe228Leu	missense	Exon 2 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.684T>G	p.Phe228Leu	missense	Exon 2 of 8	ENSP00000350574.4
	ZBTB44	ENST00000530205.5	TSL:1	c.684T>G	p.Phe228Leu	missense	Exon 1 of 6	ENSP00000434177.1	Q8NCP5-2
	ZBTB44	ENST00000525842.5	TSL:1	c.684T>G	p.Phe228Leu	missense	Exon 2 of 6	ENSP00000433457.1	Q8NCP5-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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	0.97
BayesDel_addAF	Benign	-0.029	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.014	T
Eigen	Benign	0.024
Eigen_PC	Benign	0.099
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.033	D
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.97	L
PhyloP100		3.3
PrimateAI	Pathogenic	0.83	D
PROVEAN	Benign	-0.94	N
REVEL	Benign	0.19
Sift	Benign	0.074	T
Sift4G	Uncertain	0.024	D
Polyphen		0.97	D
Vest4		0.80
MutPred		0.34		Gain of disorder (P = 0.1767)
MVP		0.21
MPC		1.3
ClinPred		0.68	D
GERP RS		3.3
PromoterAI		-0.0062	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
gMVP		0.28
Mutation Taster		=84/16	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: chr11-130131085;