chr1-173870419-A-G

Position:

• chr1-173870419-A-G

Variant summary

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

The NM_001122770.3(ZBTB37):​c.194A>G​(p.Glu65Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZBTB37 NM_001122770.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.95

Genes affected

ZBTB37 (HGNC:28365): (zinc finger and BTB domain containing 37) Enables sequence-specific double-stranded DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be part of chromatin. Predicted to be active in nucleoplasm. [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=0.1993751).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZBTB37	NM_001122770.3	c.194A>G	p.Glu65Gly	missense_variant	3/5	ENST00000367701.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZBTB37	ENST00000367701.10	c.194A>G	p.Glu65Gly	missense_variant	3/5	1	NM_001122770.3	P1
ZBTB37	ENST00000695459.1	c.194A>G	p.Glu65Gly	missense_variant	3/5			P1
ZBTB37	ENST00000367702.1	c.194A>G	p.Glu65Gly	missense_variant	3/4	5
ZBTB37	ENST00000367704.5	c.194A>G	p.Glu65Gly	missense_variant	3/4	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

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

Feb 22, 2023

The c.194A>G (p.E65G) alteration is located in exon 3 (coding exon 1) of the ZBTB37 gene. This alteration results from a A to G substitution at nucleotide position 194, causing the glutamic acid (E) at amino acid position 65 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	Pathogenic	0.64
BayesDel_addAF	Uncertain	0.073	D
BayesDel_noAF	Benign	-0.13
CADD	Pathogenic	29
DANN	Uncertain	1.0
Eigen	Uncertain	0.38
Eigen_PC	Uncertain	0.50
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.91	D;D;D;.
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.20	T;T;T;T
MetaSVM	Benign	-0.72	T
MutationAssessor	Benign	-0.055	N;N;N;N
MutationTaster	Benign	1.0	D;D;D;D;D
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	-0.090	N;N;N;N
REVEL	Uncertain	0.32
Sift	Benign	0.22	T;T;T;T
Sift4G	Benign	0.21	T;T;T;T
Polyphen		0.99, 0.97	.;D;D;D
Vest4		0.30
MutPred		0.46		Gain of catalytic residue at M61 (P = 0.0349);Gain of catalytic residue at M61 (P = 0.0349);Gain of catalytic residue at M61 (P = 0.0349);Gain of catalytic residue at M61 (P = 0.0349);
MVP		0.25
MPC		0.44
ClinPred		0.96	D
GERP RS		5.6
Varity_R		0.23
gMVP		0.68

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: chr1-173839557;