3-141443343-T-G

Position:

• chr3-141443343-T-G

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 1P and 12B. PP2 BP4_Strong BA1

The NM_001376113.1(ZBTB38):​c.955T>G​(p.Ser319Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.121 in 1,614,046 control chromosomes in the GnomAD database, including 14,112 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 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 nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.12 (1480 hom., cov: 32)
  • Exomes 𝑓: 0.12 (12632 hom.)
• Consequence: ZBTB38 NM_001376113.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.609

Genes affected

ZBTB38 (HGNC:26636): (zinc finger and BTB domain containing 38) The protein encoded by this gene is a zinc finger transcriptional activator that binds methylated DNA. The encoded protein can form homodimers or heterodimers through the zinc finger domains. In mouse, inhibition of this protein has been associated with apoptosis in some cell types. [provided by RefSeq, Jun 2010]

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• PP2: Missense variant where missense usually causes diseases, ZBTB38
• BP4: Computational evidence support a benign effect (MetaRNN=0.0043250322).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.311 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZBTB38	NM_001376113.1	c.955T>G	p.Ser319Ala	missense_variant	6/6	ENST00000321464.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZBTB38	ENST00000321464.7	c.955T>G	p.Ser319Ala	missense_variant	6/6		NM_001376113.1	P1

Frequencies

GnomAD3 genomes AF: 0.123 AC: 18752 AN: 152036 Hom.: 1479 Cov.: 32

Gnomad AFR AF: 0.0956

Gnomad AMI AF: 0.0570

Gnomad AMR AF: 0.229

Gnomad ASJ AF: 0.106

Gnomad EAS AF: 0.324

Gnomad SAS AF: 0.169

Gnomad FIN AF: 0.102

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.103

Gnomad OTH AF: 0.124

GnomAD3 exomes AF: 0.153 AC: 38131 AN: 249310 Hom.: 3812 AF XY: 0.148 AC XY: 20066 AN XY: 135312

Gnomad AFR exome AF: 0.0954

Gnomad AMR exome AF: 0.277

Gnomad ASJ exome AF: 0.0953

Gnomad EAS exome AF: 0.334

Gnomad SAS exome AF: 0.169

Gnomad FIN exome AF: 0.0907

Gnomad NFE exome AF: 0.108

Gnomad OTH exome AF: 0.131

GnomAD4 exome AF: 0.121 AC: 176640 AN: 1461892 Hom.: 12632 Cov.: 34 AF XY: 0.121 AC XY: 87993 AN XY: 727246

Gnomad4 AFR exome AF: 0.0950

Gnomad4 AMR exome AF: 0.270

Gnomad4 ASJ exome AF: 0.0942

Gnomad4 EAS exome AF: 0.340

Gnomad4 SAS exome AF: 0.169

Gnomad4 FIN exome AF: 0.0891

Gnomad4 NFE exome AF: 0.106

Gnomad4 OTH exome AF: 0.122

GnomAD4 genome AF: 0.123 AC: 18769 AN: 152154 Hom.: 1480 Cov.: 32 AF XY: 0.128 AC XY: 9547 AN XY: 74386

Gnomad4 AFR AF: 0.0960

Gnomad4 AMR AF: 0.229

Gnomad4 ASJ AF: 0.106

Gnomad4 EAS AF: 0.324

Gnomad4 SAS AF: 0.168

Gnomad4 FIN AF: 0.102

Gnomad4 NFE AF: 0.103

Gnomad4 OTH AF: 0.129

Alfa AF: 0.112 Hom.: 2205

Bravo AF: 0.130

TwinsUK AF: 0.103 AC: 382

ALSPAC AF: 0.108 AC: 415

ESP6500AA AF: 0.0977 AC: 372

ESP6500EA AF: 0.105 AC: 862

ExAC AF: 0.148 AC: 17950

Asia WGS AF: 0.214 AC: 741 AN: 3478

EpiCase AF: 0.103

EpiControl AF: 0.0985

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.074
BayesDel_addAF	Benign	-0.81	T
BayesDel_noAF	Benign	-0.79
CADD	Benign	3.6
DANN	Benign	0.86
DEOGEN2	Benign	0.020	T;.;T;T;T;T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.33	N
LIST_S2	Benign	0.28	T;T;.;.;.;T
MetaRNN	Benign	0.0043	T;T;T;T;T;T
MetaSVM	Benign	-0.90	T
MutationTaster	Benign	1.0	P;P;P
PrimateAI	Benign	0.26	T
Polyphen		0.018	.;.;B;B;B;B
Vest4		0.035, 0.030, 0.026
MPC		0.35
ClinPred		0.0055	T
GERP RS		-2.6
Varity_R		0.032
gMVP		0.13

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: rs16851435; hg19: chr3-141162185; COSMIC: COSV58540798; COSMIC: COSV58540798;