18-48029535-T-C

Variant summary

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

The NM_001318841.2(ZBTB7C):c.1585A>G(p.Ser529Gly) 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. 13/21 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: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ZBTB7C NM_001318841.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.90

Genes affected

ZBTB7C (HGNC:31700): (zinc finger and BTB domain containing 7C) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Involved in negative regulation of cell population proliferation. Predicted to be located in nucleus. [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=0.12367204).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZBTB7C	NM_001318841.2	c.1585A>G	p.Ser529Gly	missense_variant	5/5	ENST00000590800.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZBTB7C	ENST00000590800.6	c.1585A>G	p.Ser529Gly	missense_variant	5/5	1	NM_001318841.2	P1
ZBTB7C	ENST00000535628.6	c.1585A>G	p.Ser529Gly	missense_variant	3/3	1		P1
ZBTB7C	ENST00000586438.5	c.1585A>G	p.Ser529Gly	missense_variant	3/3	1		P1
ZBTB7C	ENST00000588982.5	c.1585A>G	p.Ser529Gly	missense_variant	4/4	1		P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1418612 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 705718

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: 0.00

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

Dec 19, 2022

The c.1585A>G (p.S529G) alteration is located in exon 3 (coding exon 2) of the ZBTB7C gene. This alteration results from a A to G substitution at nucleotide position 1585, causing the serine (S) at amino acid position 529 to be replaced by a glycine (G). 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	-0.16	T
BayesDel_noAF	Benign	-0.46
Cadd	Benign	19
Dann	Uncertain	1.0
DEOGEN2	Benign	0.0091	T;T;T;T
Eigen	Benign	-0.30
Eigen_PC	Benign	-0.12
FATHMM_MKL	Uncertain	0.92	D
M_CAP	Benign	0.062	D
MetaRNN	Benign	0.12	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.90	L;L;L;L
MutationTaster	Benign	1.0	D;D;D;D;D
PrimateAI	Pathogenic	0.81	D
PROVEAN	Benign	-0.22	N;.;.;.
REVEL	Benign	0.072
Sift	Uncertain	0.011	D;.;.;.
Sift4G	Benign	0.21	T;T;T;T
Polyphen		0.023	B;B;B;B
Vest4		0.21
MutPred		0.29		Loss of phosphorylation at S529 (P = 0.0637);Loss of phosphorylation at S529 (P = 0.0637);Loss of phosphorylation at S529 (P = 0.0637);Loss of phosphorylation at S529 (P = 0.0637);
MVP		0.082
MPC		1.0
ClinPred		0.93	D
GERP RS		4.5
Varity_R		0.29
gMVP		0.28

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: chr18-45555906;