11-130239872-T-C

Variant names:

• chr11-130239872-T-C
• rs1341293720
• NM_001301098.2:c.1043A>G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001301098.2(ZBTB44):​c.1043A>G​(p.Glu348Gly) 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: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ZBTB44 NM_001301098.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.20

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 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZBTB44	NM_001301098.2	c.1043A>G	p.Glu348Gly	missense_variant	Exon 3 of 8	ENST00000357899.9	NP_001288027.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZBTB44	ENST00000357899.9	c.1043A>G	p.Glu348Gly	missense_variant	Exon 3 of 8	1	NM_001301098.2	ENSP00000350574.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1459526 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 725746

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

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 19, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1043A>G (p.E348G) alteration is located in exon 3 (coding exon 2) of the ZBTB44 gene. This alteration results from a A to G substitution at nucleotide position 1043, causing the glutamic acid (E) at amino acid position 348 to be replaced by a glycine (G). 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	Benign	0.19
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.060
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.022	.;.;T;T;.
Eigen	Benign	0.10
Eigen_PC	Benign	0.16
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.96	D;D;D;.;D
M_CAP	Benign	0.057	D
MetaRNN	Uncertain	0.44	T;T;T;T;T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	0.97	.;L;.;.;L
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-1.7	.;N;N;N;N
REVEL	Uncertain	0.31
Sift	Uncertain	0.0070	.;D;D;D;T
Sift4G	Benign	0.24	.;T;T;T;T
Polyphen		0.73, 0.88	.;P;.;.;P
Vest4		0.79, 0.76, 0.77, 0.72
MutPred		0.28		Loss of solvent accessibility (P = 0.0017);Loss of solvent accessibility (P = 0.0017);Loss of solvent accessibility (P = 0.0017);Loss of solvent accessibility (P = 0.0017);Loss of solvent accessibility (P = 0.0017);
MVP		0.29
MPC		0.92
ClinPred		0.86	D
GERP RS		5.5
gMVP		0.48

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

LitVar

Other links and lift over

dbSNP: rs1341293720; hg19: chr11-130109767;