11-130261190-A-C

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 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. 12/20 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

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZBTB44	NM_001301098.2	c.684T>G	p.Phe228Leu	missense_variant	Exon 2 of 8	ENST00000357899.9	NP_001288027.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZBTB44	ENST00000357899.9	c.684T>G	p.Phe228Leu	missense_variant	Exon 2 of 8	1	NM_001301098.2	ENSP00000350574.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Oct 05, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.684T>G (p.F228L) alteration is located in exon 2 (coding exon 1) of the ZBTB44 gene. This alteration results from a T to G substitution at nucleotide position 684, causing the phenylalanine (F) at amino acid position 228 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

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;T;.
Eigen	Benign	0.024
Eigen_PC	Benign	0.099
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.96	D;D;D;.;D
M_CAP	Benign	0.033	D
MetaRNN	Benign	0.20	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.97	.;L;.;.;L
PrimateAI	Pathogenic	0.83	D
PROVEAN	Benign	-0.94	.;N;N;N;N
REVEL	Benign	0.19
Sift	Benign	0.074	.;T;T;T;T
Sift4G	Uncertain	0.024	.;D;D;D;D
Polyphen		0.97	.;D;.;.;D
Vest4		0.80, 0.64, 0.65, 0.70
MutPred		0.34		Gain of disorder (P = 0.1767);Gain of disorder (P = 0.1767);Gain of disorder (P = 0.1767);Gain of disorder (P = 0.1767);Gain of disorder (P = 0.1767);
MVP		0.21
MPC		1.3
ClinPred		0.68	D
GERP RS		3.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
gMVP		0.28

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: chr11-130131085;