rs777917847

Variant names:

• chr3-141442761-C-A
• rs777917847
• NM_001376113.1:c.373C>A

Your query was ambiguous. Multiple possible variants found:

• chr3-141442761-C-A
• chr3-141442761-C-T

Variant summary

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

The NM_001376113.1(ZBTB38):​c.373C>A​(p.Arg125Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000144 in 1,461,874 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 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. R125C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000014 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ZBTB38 NM_001376113.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0860

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 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=0.048835635).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZBTB38	NM_001376113.1	c.373C>A	p.Arg125Ser	missense_variant	Exon 6 of 6	ENST00000321464.7	NP_001363042.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZBTB38	ENST00000321464.7	c.373C>A	p.Arg125Ser	missense_variant	Exon 6 of 6	6	NM_001376113.1	ENSP00000372635.5

Frequencies

GnomAD3 genomes AF: 0.00 AC: 1 AN: 152082 Hom.: 0 Cov.: 32 FAILED QC

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.0000361 AC: 9 AN: 249464 Hom.: 1 AF XY: 0.0000443 AC XY: 6 AN XY: 135344

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: 0.000294

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000144 AC: 21 AN: 1461874 Hom.: 0 Cov.: 32 AF XY: 0.0000234 AC XY: 17 AN XY: 727240

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: 0.000243

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000657 AC: 1 AN: 152200 Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1 AN XY: 74400

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000208

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ExAC AF: 0.0000248 AC: 3

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.33
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	17
DANN	Benign	0.67
DEOGEN2	Benign	0.14	T;T;.;T;T;T;T;.;T
Eigen	Benign	-0.64
Eigen_PC	Benign	-0.47
FATHMM_MKL	Benign	0.48	N
LIST_S2	Benign	0.67	T;T;T;.;.;T;.;T;T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.049	T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.40	.;.;.;N;N;.;N;.;N
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.67	N;.;N;N;.;N;N;N;.
REVEL	Benign	0.13
Sift	Benign	0.25	T;.;T;T;.;T;T;T;.
Sift4G	Benign	0.76	T;.;T;T;.;T;T;T;T
Polyphen		0.0020	.;.;.;B;B;.;B;.;B
Vest4		0.082, 0.079, 0.084
MutPred		0.51		Gain of disorder (P = 0.0597);Gain of disorder (P = 0.0597);Gain of disorder (P = 0.0597);Gain of disorder (P = 0.0597);Gain of disorder (P = 0.0597);Gain of disorder (P = 0.0597);Gain of disorder (P = 0.0597);Gain of disorder (P = 0.0597);Gain of disorder (P = 0.0597);
MVP		0.22
MPC		0.48
ClinPred		0.44	T
GERP RS		2.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.098
gMVP		0.71

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: rs777917847; hg19: chr3-141161603; COSMIC: COSV58539977; COSMIC: COSV58539977;