3-141443343-T-G

Variant names:

• chr3-141443343-T-G
• rs16851435
• NM_001376113.1:c.955T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. 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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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
• Publications: 23 publications found

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]

ENSG00000288585 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001376113.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZBTB38	NM_001376113.1	MANE Select	c.955T>G	p.Ser319Ala	missense	Exon 6 of 6	NP_001363042.1	Q8NAP3
	ZBTB38	NM_001080412.3		c.955T>G	p.Ser319Ala	missense	Exon 8 of 8	NP_001073881.2	Q8NAP3
	ZBTB38	NM_001350099.2		c.955T>G	p.Ser319Ala	missense	Exon 6 of 6	NP_001337028.1	Q8NAP3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZBTB38	ENST00000321464.7	TSL:6 MANE Select	c.955T>G	p.Ser319Ala	missense	Exon 6 of 6	ENSP00000372635.5	Q8NAP3
	ZBTB38	ENST00000509883.5	TSL:1	c.955T>G	p.Ser319Ala	missense	Exon 3 of 3	ENSP00000424254.1	D6RBC4
	ZBTB38	ENST00000441582.2	TSL:2	c.955T>G	p.Ser319Ala	missense	Exon 2 of 2	ENSP00000406955.2	Q8NAP3

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

GnomAD2 exomes AF: 0.153 AC: 38131 AN: 249310 AF XY: 0.148

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 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

African (AFR) AF: 0.0950 AC: 3180 AN: 33480

American (AMR) AF: 0.270 AC: 12074 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0942 AC: 2463 AN: 26136

East Asian (EAS) AF: 0.340 AC: 13517 AN: 39700

South Asian (SAS) AF: 0.169 AC: 14580 AN: 86258

European-Finnish (FIN) AF: 0.0891 AC: 4762 AN: 53420

Middle Eastern (MID) AF: 0.110 AC: 637 AN: 5768

European-Non Finnish (NFE) AF: 0.106 AC: 118087 AN: 1112010

Other (OTH) AF: 0.122 AC: 7340 AN: 60396

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

African (AFR) AF: 0.0960 AC: 3986 AN: 41510

American (AMR) AF: 0.229 AC: 3494 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.106 AC: 369 AN: 3470

East Asian (EAS) AF: 0.324 AC: 1667 AN: 5150

South Asian (SAS) AF: 0.168 AC: 810 AN: 4824

European-Finnish (FIN) AF: 0.102 AC: 1082 AN: 10598

Middle Eastern (MID) AF: 0.139 AC: 41 AN: 294

European-Non Finnish (NFE) AF: 0.103 AC: 6995 AN: 67996

Other (OTH) AF: 0.129 AC: 273 AN: 2112

Alfa AF: 0.114 Hom.: 4477

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 v4.9

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
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.33	N
LIST_S2	Benign	0.28	T
MetaRNN	Benign	0.0043	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	1.9	L
PhyloP100		-0.61
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.68	N
REVEL	Benign	0.033
Sift	Benign	0.11	T
Sift4G	Benign	0.22	T
Polyphen		0.018	B
Vest4		0.035
MPC		0.35
ClinPred		0.0055	T
GERP RS		-2.6
Varity_R		0.032
gMVP		0.13
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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