20-63747082-C-T

Variant names:

• chr20-63747082-C-T
• NM_001369741.1:c.1618G>A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001369741.1(ZBTB46):​c.1618G>A​(p.Asp540Asn) variant causes a missense change. The variant allele was found at a frequency of 0.000000686 in 1,457,234 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. D540Y) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 28)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: ZBTB46 NM_001369741.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.11

Genes affected

ZBTB46 (HGNC:16094): (zinc finger and BTB domain containing 46) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and 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 act upstream of or within regulation of leukocyte differentiation. Predicted to be part of chromatin. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.30606264).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZBTB46	NM_001369741.1	c.1618G>A	p.Asp540Asn	missense_variant	Exon 5 of 5	ENST00000245663.9	NP_001356670.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZBTB46	ENST00000245663.9	c.1618G>A	p.Asp540Asn	missense_variant	Exon 5 of 5	5	NM_001369741.1	ENSP00000245663.3
ZBTB46	ENST00000302995.2	c.1618G>A	p.Asp540Asn	missense_variant	Exon 5 of 7	2		ENSP00000303102.2
ZBTB46	ENST00000395104.5	c.1618G>A	p.Asp540Asn	missense_variant	Exon 4 of 4	2		ENSP00000378536.1

Frequencies

GnomAD3 genomes Cov.: 28

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1457234 Hom.: 0 Cov.: 43 AF XY: 0.00000138 AC XY: 1 AN XY: 725132

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: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 28

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.053	T;T;T
Eigen	Benign	-0.022
Eigen_PC	Benign	-0.048
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.64	.;.;T
M_CAP	Benign	0.048	D
MetaRNN	Benign	0.31	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.1	M;M;M
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	-1.2	N;N;N
REVEL	Benign	0.092
Sift	Benign	0.11	T;T;T
Sift4G	Benign	0.18	T;T;T
Polyphen		0.88	P;P;P
Vest4		0.38
MutPred		0.36		Gain of helix (P = 0.0325);Gain of helix (P = 0.0325);Gain of helix (P = 0.0325);
MVP		0.22
MPC		0.34
ClinPred		0.96	D
GERP RS		4.0
Varity_R		0.13
gMVP		0.27

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: chr20-62378435;