1-173885823-G-T

Position:

• chr1-173885823-G-T

Variant summary

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

The NM_001122770.3(ZBTB37):​c.1211G>T​(p.Arg404Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZBTB37 NM_001122770.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.16

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZBTB37	NM_001122770.3	c.1211G>T	p.Arg404Leu	missense_variant	5/5	ENST00000367701.10	NP_001116242.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZBTB37	ENST00000367701.10	c.1211G>T	p.Arg404Leu	missense_variant	5/5	1	NM_001122770.3	ENSP00000356674	P1
ZBTB37	ENST00000695459.1	c.1211G>T	p.Arg404Leu	missense_variant	5/5			ENSP00000511931	P1
ZBTB37	ENST00000367704.5	c.*184G>T		3_prime_UTR_variant	4/4	2		ENSP00000356677

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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

Aug 13, 2021

The c.1211G>T (p.R404L) alteration is located in exon 5 (coding exon 3) of the ZBTB37 gene. This alteration results from a G to T substitution at nucleotide position 1211, causing the arginine (R) at amino acid position 404 to be replaced by a leucine (L). 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	0.85
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.080
CADD	Pathogenic	32
DANN	Uncertain	1.0
DEOGEN2	Benign	0.024	T;T
Eigen	Pathogenic	0.69
Eigen_PC	Pathogenic	0.74
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.79	T;.
M_CAP	Benign	0.0080	T
MetaRNN	Uncertain	0.71	D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.41	N;N
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Pathogenic	0.93	D
PROVEAN	Benign	-1.8	N;N
REVEL	Uncertain	0.38
Sift	Uncertain	0.022	D;D
Sift4G	Benign	0.11	T;T
Polyphen		1.0	D;D
Vest4		0.66
MutPred		0.56		Loss of MoRF binding (P = 0.003);Loss of MoRF binding (P = 0.003);
MVP		0.38
MPC		0.98
ClinPred		0.93	D
GERP RS		5.8
Varity_R		0.31
gMVP		0.80

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: chr1-173854961;