10-38117897-G-A

Position:

• chr10-38117897-G-A

Variant summary

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

The NM_001324250.3(ZNF37A):​c.746G>A​(p.Gly249Glu) 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. 14/21 in silico tools predict 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: 1.60

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=0.28526127).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF37A	NM_001324250.3	c.746G>A	p.Gly249Glu	missense_variant	8/8	ENST00000685332.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF37A	ENST00000685332.1	c.746G>A	p.Gly249Glu	missense_variant	8/8		NM_001324250.3	P1
ZNF37A	ENST00000351773.7	c.746G>A	p.Gly249Glu	missense_variant	8/8	1		P1
ZNF37A	ENST00000361085.9	c.746G>A	p.Gly249Glu	missense_variant	7/7	2		P1
ZNF37A	ENST00000638053.1	c.238+2607G>A		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

May 09, 2023

The c.746G>A (p.G249E) alteration is located in exon 8 (coding exon 4) of the ZNF37A gene. This alteration results from a G to A substitution at nucleotide position 746, causing the glycine (G) at amino acid position 249 to be replaced by a glutamic acid (E). 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	0.13
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	10
DANN	Benign	0.97
DEOGEN2	Benign	0.12	T;T
Eigen	Benign	-0.31
Eigen_PC	Benign	-0.39
FATHMM_MKL	Benign	0.00078	N
LIST_S2	Benign	0.56	T;.
M_CAP	Benign	0.0043	T
MetaRNN	Benign	0.29	T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	2.0	M;M
MutationTaster	Benign	0.80	N;N
PrimateAI	Benign	0.41	T
PROVEAN	Pathogenic	-4.9	D;D
REVEL	Benign	0.12
Sift	Uncertain	0.018	D;D
Sift4G	Benign	0.068	T;T
Polyphen		0.35	B;B
Vest4		0.26
MutPred		0.66		Loss of catalytic residue at S253 (P = 0.2449);Loss of catalytic residue at S253 (P = 0.2449);
MVP		0.57
MPC		0.088
ClinPred		0.29	T
GERP RS		2.0
Varity_R		0.20
gMVP		0.036

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: chr10-38406825;