4-4302041-G-A

Position:

• chr4-4302041-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_145291.4(ZBTB49):​c.205G>A​(p.Val69Ile) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZBTB49 NM_145291.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.21

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.03636515).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZBTB49	NM_145291.4	c.205G>A	p.Val69Ile	missense_variant	3/8	ENST00000337872.9	NP_660334.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZBTB49	ENST00000337872.9	c.205G>A	p.Val69Ile	missense_variant	3/8	1	NM_145291.4	ENSP00000338807.4
ZBTB49	ENST00000515012.5	n.205G>A		non_coding_transcript_exon_variant	3/6	1		ENSP00000422321.1
ZBTB49	ENST00000503703.5	n.153-270G>A		intron_variant		1		ENSP00000424525.1
ZBTB49	ENST00000502918.1	c.205G>A	p.Val69Ile	missense_variant	3/3	3		ENSP00000425747.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 33

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 25, 2024

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.098
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	6.6
DANN	Benign	0.53
DEOGEN2	Benign	0.037	T;.
Eigen	Benign	-1.1
Eigen_PC	Benign	-0.90
FATHMM_MKL	Benign	0.63	D
LIST_S2	Benign	0.79	T;T
M_CAP	Benign	0.0086	T
MetaRNN	Benign	0.036	T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	-1.7	N;.
PrimateAI	Benign	0.26	T
PROVEAN	Benign	0.13	N;N
REVEL	Benign	0.12
Sift	Benign	1.0	T;T
Sift4G	Benign	1.0	T;T
Polyphen		0.0	B;.
Vest4		0.044
MutPred		0.39		Loss of ubiquitination at K70 (P = 0.1151);Loss of ubiquitination at K70 (P = 0.1151);
MVP		0.35
MPC		0.12
ClinPred		0.059	T
GERP RS		-0.087
Varity_R		0.028
gMVP		0.11

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr4-4303768;