19-35715026-C-T

Variant names:

• chr19-35715026-C-T
• rs767597336
• NM_014383.3:c.400C>T

Variant summary

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

The NM_014383.3(ZBTB32):​c.400C>T​(p.Pro134Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,210 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P134T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ZBTB32 NM_014383.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.292

Genes affected

ZBTB32 (HGNC:16763): (zinc finger and BTB domain containing 32) Enables DNA-binding transcription repressor activity, RNA polymerase II-specific; identical protein binding activity; and sequence-specific double-stranded DNA binding activity. Involved in negative regulation of transcription by RNA polymerase II. Located in nucleus. [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=0.053474605).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZBTB32	NM_014383.3	c.400C>T	p.Pro134Ser	missense_variant	Exon 3 of 7	ENST00000392197.7	NP_055198.1
ZBTB32	NM_001316902.2	c.6-437C>T		intron_variant	Intron 2 of 6		NP_001303831.1
ZBTB32	NM_001316903.2	c.-86-437C>T		intron_variant	Intron 2 of 5		NP_001303832.1
ZBTB32	XM_017026591.2	c.6-437C>T		intron_variant	Intron 2 of 5		XP_016882080.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZBTB32	ENST00000392197.7	c.400C>T	p.Pro134Ser	missense_variant	Exon 3 of 7	5	NM_014383.3	ENSP00000376035.1
ZBTB32	ENST00000262630.7	c.400C>T	p.Pro134Ser	missense_variant	Exon 2 of 6	1		ENSP00000262630.3
ZBTB32	ENST00000481182.1	n.400C>T		non_coding_transcript_exon_variant	Exon 2 of 4	1		ENSP00000433657.1
ZBTB32	ENST00000426659.6	c.-86-437C>T		intron_variant	Intron 2 of 5	3		ENSP00000466524.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000808 AC: 2 AN: 247534 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 134172

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000655

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460210 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 726508

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

ExAC AF: 0.0000247 AC: 3

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	9.9
DANN	Uncertain	0.99
DEOGEN2	Benign	0.17	T;T
Eigen	Benign	-0.79
Eigen_PC	Benign	-0.76
FATHMM_MKL	Benign	0.055	N
LIST_S2	Benign	0.64	.;T
M_CAP	Benign	0.0066	T
MetaRNN	Benign	0.053	T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.8	L;L
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-0.60	N;N
REVEL	Benign	0.019
Sift	Uncertain	0.026	D;D
Sift4G	Benign	0.40	T;T
Polyphen		0.062	B;B
Vest4		0.11
MutPred		0.19		Gain of phosphorylation at P134 (P = 0.0024);Gain of phosphorylation at P134 (P = 0.0024);
MVP		0.28
MPC		0.31
ClinPred		0.18	T
GERP RS		3.0
Varity_R		0.033
gMVP		0.17

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: rs767597336; hg19: chr19-36205928;