10-38118401-G-A

Position:

• chr10-38118401-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.1250G>A​(p.Gly417Glu) 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: 1.93

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=0.34222347).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF37A	NM_001324250.3	c.1250G>A	p.Gly417Glu	missense_variant	8/8	ENST00000685332.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF37A	ENST00000685332.1	c.1250G>A	p.Gly417Glu	missense_variant	8/8		NM_001324250.3	P1
ZNF37A	ENST00000351773.7	c.1250G>A	p.Gly417Glu	missense_variant	8/8	1		P1
ZNF37A	ENST00000361085.9	c.1250G>A	p.Gly417Glu	missense_variant	7/7	2		P1
ZNF37A	ENST00000638053.1	c.238+3111G>A		intron_variant		5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000312 Hom.: 0

Bravo AF: 0.00000378

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

Sep 23, 2023

The c.1250G>A (p.G417E) 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 1250, causing the glycine (G) at amino acid position 417 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	Pathogenic	0.65
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.086	T;T
Eigen	Uncertain	0.30
Eigen_PC	Benign	0.21
FATHMM_MKL	Benign	0.0029	N
LIST_S2	Benign	0.19	T;.
M_CAP	Benign	0.0045	T
MetaRNN	Benign	0.34	T;T
MetaSVM	Benign	-0.87	T
MutationAssessor	Benign	0.90	L;L
MutationTaster	Benign	0.89	D;D
PrimateAI	Benign	0.40	T
PROVEAN	Pathogenic	-7.0	D;D
REVEL	Benign	0.14
Sift	Uncertain	0.0020	D;D
Sift4G	Uncertain	0.023	D;D
Polyphen		0.99	D;D
Vest4		0.20
MutPred		0.68		Gain of phosphorylation at S419 (P = 0.1261);Gain of phosphorylation at S419 (P = 0.1261);
MVP		0.50
MPC		0.16
ClinPred		0.94	D
GERP RS		2.3
Varity_R		0.64
gMVP		0.019

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

LitVar

Other links and lift over

dbSNP: rs2069465506; hg19: chr10-38407329;