chr10-38118368-C-T

Position:

• chr10-38118368-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001324250.3(ZNF37A):​c.1217C>T​(p.Thr406Ile) variant causes a missense change involving the alteration of a non-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: ZNF37A NM_001324250.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.49

Genes affected

ZNF37A (HGNC:13102): (zinc finger protein 37A) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.36320683).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF37A	NM_001324250.3	c.1217C>T	p.Thr406Ile	missense_variant	8/8	ENST00000685332.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF37A	ENST00000685332.1	c.1217C>T	p.Thr406Ile	missense_variant	8/8		NM_001324250.3	P1
ZNF37A	ENST00000351773.7	c.1217C>T	p.Thr406Ile	missense_variant	8/8	1		P1
ZNF37A	ENST00000361085.9	c.1217C>T	p.Thr406Ile	missense_variant	7/7	2		P1
ZNF37A	ENST00000638053.1	c.238+3078C>T		intron_variant		5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

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

Apr 05, 2023

The c.1217C>T (p.T406I) alteration is located in exon 8 (coding exon 4) of the ZNF37A gene. This alteration results from a C to T substitution at nucleotide position 1217, causing the threonine (T) at amino acid position 406 to be replaced by an isoleucine (I). 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	0.78
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	18
DANN	Uncertain	1.0
DEOGEN2	Benign	0.14	T;T
Eigen	Uncertain	0.28
Eigen_PC	Benign	0.15
FATHMM_MKL	Benign	0.0012	N
LIST_S2	Benign	0.11	T;.
M_CAP	Benign	0.0046	T
MetaRNN	Benign	0.36	T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.6	L;L
MutationTaster	Benign	0.69	N;N
PrimateAI	Uncertain	0.57	T
PROVEAN	Pathogenic	-5.6	D;D
REVEL	Benign	0.092
Sift	Benign	0.048	D;D
Sift4G	Uncertain	0.012	D;D
Polyphen		0.99	D;D
Vest4		0.24
MutPred		0.42		Loss of phosphorylation at T406 (P = 0.0506);Loss of phosphorylation at T406 (P = 0.0506);
MVP		0.43
MPC		0.25
ClinPred		0.98	D
GERP RS		1.4
Varity_R		0.17
gMVP		0.034

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: chr10-38407296;