chr1-32593562-A-C

Position:

• chr1-32593562-A-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.631A>C​(p.Lys211Gln) 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. 14/19 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: ZBTB8A NM_001040441.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.63

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=0.1260694).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZBTB8A	NM_001040441.3	c.631A>C	p.Lys211Gln	missense_variant	3/5	ENST00000373510.9	NP_001035531.2
ZBTB8A	NM_001291496.2	c.631A>C	p.Lys211Gln	missense_variant	3/5		NP_001278425.1
ZBTB8A	NR_111980.2	n.229-1492A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZBTB8A	ENST00000373510.9	c.631A>C	p.Lys211Gln	missense_variant	3/5	1	NM_001040441.3	ENSP00000362609.3
ZBTB8A	ENST00000316459.4	c.631A>C	p.Lys211Gln	missense_variant	3/5	1		ENSP00000317561.4
ENSG00000254553	ENST00000480336.1	n.*750A>C		non_coding_transcript_exon_variant	8/10	2		ENSP00000455300.1
ENSG00000254553	ENST00000480336.1	n.*750A>C		3_prime_UTR_variant	8/10	2		ENSP00000455300.1

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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 20, 2023

The c.631A>C (p.K211Q) alteration is located in exon 3 (coding exon 1) of the ZBTB8A gene. This alteration results from a A to C substitution at nucleotide position 631, causing the lysine (K) at amino acid position 211 to be replaced by a glutamine (Q). 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	0.16
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	19
DANN	Benign	0.97
DEOGEN2	Benign	0.012	.;T
Eigen	Benign	-0.29
Eigen_PC	Benign	-0.090
FATHMM_MKL	Benign	0.59	D
LIST_S2	Benign	0.84	.;T
M_CAP	Benign	0.0041	T
MetaRNN	Benign	0.13	T;T
MetaSVM	Benign	-1.0	T
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-0.37	N;N
REVEL	Benign	0.035
Sift	Benign	0.23	T;T
Sift4G	Benign	0.50	T;T
Polyphen		0.090	.;B
Vest4		0.28
MutPred		0.26		Loss of methylation at K211 (P = 0.0072);Loss of methylation at K211 (P = 0.0072);
MVP		0.15
MPC		0.69
ClinPred		0.15	T
GERP RS		5.0
gMVP		0.16

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: chr1-33059163;