chr1-173885753-T-A

Position:

• chr1-173885753-T-A

Variant summary

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

The NM_001122770.3(ZBTB37):​c.1141T>A​(p.Ser381Thr) variant causes a missense change. 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: 6.14

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	UniProt
ZBTB37	NM_001122770.3	c.1141T>A	p.Ser381Thr	missense_variant	5/5	ENST00000367701.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZBTB37	ENST00000367701.10	c.1141T>A	p.Ser381Thr	missense_variant	5/5	1	NM_001122770.3	P1
ZBTB37	ENST00000695459.1	c.1141T>A	p.Ser381Thr	missense_variant	5/5			P1
ZBTB37	ENST00000367704.5	c.*114T>A		3_prime_UTR_variant	4/4	2

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

Jun 09, 2022

The c.1141T>A (p.S381T) alteration is located in exon 5 (coding exon 3) of the ZBTB37 gene. This alteration results from a T to A substitution at nucleotide position 1141, causing the serine (S) at amino acid position 381 to be replaced by a threonine (T). 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	Benign	0.31
BayesDel_addAF	Uncertain	0.023	T
BayesDel_noAF	Benign	-0.21
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.016	T;T
Eigen	Uncertain	0.51
Eigen_PC	Uncertain	0.56
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.81	T;.
M_CAP	Benign	0.024	T
MetaRNN	Uncertain	0.44	T;T
MetaSVM	Benign	-0.48	T
MutationAssessor	Benign	1.5	L;L
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Pathogenic	0.93	D
PROVEAN	Benign	-0.71	N;N
REVEL	Uncertain	0.31
Sift	Benign	0.39	T;T
Sift4G	Benign	0.062	T;T
Polyphen		0.98	D;D
Vest4		0.42
MutPred		0.38		Gain of methylation at K385 (P = 0.1085);Gain of methylation at K385 (P = 0.1085);
MVP		0.62
MPC		0.38
ClinPred		0.84	D
GERP RS		5.8
Varity_R		0.26
gMVP		0.61

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: chr1-173854891;