4-4302936-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_145291.4(ZBTB49):c.1100T>G(p.Phe367Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,894 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ZBTB49 NM_145291.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.913

Genes affected

ZBTB49 (HGNC:19883): (zinc finger and BTB domain containing 49) Enables DNA-binding transcription factor binding activity; sequence-specific DNA binding activity; and transcription coactivator binding activity. Involved in negative regulation of cell population proliferation; positive regulation of transcription by RNA polymerase II; and regulation of cell cycle. Located in cytosol; microtubule cytoskeleton; and nucleoplasm. [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=0.2077629).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZBTB49	NM_145291.4	c.1100T>G	p.Phe367Cys	missense_variant	3/8	ENST00000337872.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZBTB49	ENST00000337872.9	c.1100T>G	p.Phe367Cys	missense_variant	3/8	1	NM_145291.4	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461894 Hom.: 0 Cov.: 34 AF XY: 0.00000138 AC XY: 1 AN XY: 727248

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: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 19, 2024

The c.1100T>G (p.F367C) alteration is located in exon 3 (coding exon 2) of the ZBTB49 gene. This alteration results from a T to G substitution at nucleotide position 1100, causing the phenylalanine (F) at amino acid position 367 to be replaced by a cysteine (C). 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	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
Cadd	Benign	9.6
Dann	Benign	0.94
DEOGEN2	Benign	0.0038	T
Eigen	Benign	-0.73
Eigen_PC	Benign	-0.89
FATHMM_MKL	Benign	0.17	N
LIST_S2	Benign	0.70	T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Uncertain	2.2	M
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-0.35	N
REVEL	Benign	0.086
Sift	Uncertain	0.027	D
Sift4G	Benign	0.13	T
Polyphen		0.69	P
Vest4		0.46
MutPred		0.52		Gain of glycosylation at S363 (P = 0.019);
MVP		0.28
MPC		0.44
ClinPred		0.33	T
GERP RS		-0.49
Varity_R		0.081
gMVP		0.097

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: chr4-4304663;