chr1-32593361-G-C

Position:

• chr1-32593361-G-C

Variant summary

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

The NM_001040441.3(ZBTB8A):​c.430G>C​(p.Gly144Arg) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZBTB8A NM_001040441.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.24

Genes affected

ZBTB8A (HGNC:24172): (zinc finger and BTB domain containing 8A) Predicted to enable RNA polymerase II transcription regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000254553 (HGNC:):

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=0.23049793).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZBTB8A	NM_001040441.3	c.430G>C	p.Gly144Arg	missense_variant	3/5	ENST00000373510.9	NP_001035531.2
ZBTB8A	NM_001291496.2	c.430G>C	p.Gly144Arg	missense_variant	3/5		NP_001278425.1
ZBTB8A	NR_111980.2	n.229-1693G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZBTB8A	ENST00000373510.9	c.430G>C	p.Gly144Arg	missense_variant	3/5	1	NM_001040441.3	ENSP00000362609.3
ZBTB8A	ENST00000316459.4	c.430G>C	p.Gly144Arg	missense_variant	3/5	1		ENSP00000317561.4
ENSG00000254553	ENST00000480336.1	n.*549G>C		non_coding_transcript_exon_variant	8/10	2		ENSP00000455300.1
ENSG00000254553	ENST00000480336.1	n.*549G>C		3_prime_UTR_variant	8/10	2		ENSP00000455300.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

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

Nov 09, 2022

The c.430G>C (p.G144R) alteration is located in exon 3 (coding exon 1) of the ZBTB8A gene. This alteration results from a G to C substitution at nucleotide position 430, causing the glycine (G) at amino acid position 144 to be replaced by an arginine (R). 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	0.22
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	20
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.021	.;T
Eigen	Uncertain	0.20
Eigen_PC	Uncertain	0.28
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.86	.;D
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.23	T;T
MetaSVM	Benign	-1.1	T
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-2.4	N;D
REVEL	Benign	0.075
Sift	Benign	0.63	T;T
Sift4G	Benign	0.081	T;T
Polyphen		1.0	.;D
Vest4		0.56
MVP		0.43
MPC		1.2
ClinPred		0.93	D
GERP RS		4.4
gMVP		0.60

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

LitVar

Other links and lift over

dbSNP: rs1187707212; hg19: chr1-33058962;