10-38117762-A-T

Position:

• chr10-38117762-A-T

Variant summary

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

The NM_001324250.3(ZNF37A):​c.611A>T​(p.Glu204Val) 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. 13/21 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: 1.15

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=0.26766324).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF37A	NM_001324250.3	c.611A>T	p.Glu204Val	missense_variant	8/8	ENST00000685332.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF37A	ENST00000685332.1	c.611A>T	p.Glu204Val	missense_variant	8/8		NM_001324250.3	P1
ZNF37A	ENST00000351773.7	c.611A>T	p.Glu204Val	missense_variant	8/8	1		P1
ZNF37A	ENST00000361085.9	c.611A>T	p.Glu204Val	missense_variant	7/7	2		P1
ZNF37A	ENST00000638053.1	c.238+2472A>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

Jan 04, 2022

The c.611A>T (p.E204V) alteration is located in exon 8 (coding exon 4) of the ZNF37A gene. This alteration results from a A to T substitution at nucleotide position 611, causing the glutamic acid (E) at amino acid position 204 to be replaced by a valine (V). 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	0.095
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.075	T;T
Eigen	Benign	-0.20
Eigen_PC	Benign	-0.45
FATHMM_MKL	Benign	0.00011	N
LIST_S2	Benign	0.11	T;.
M_CAP	Benign	0.0022	T
MetaRNN	Benign	0.27	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	L;L
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.24	T
PROVEAN	Pathogenic	-4.7	D;D
REVEL	Benign	0.036
Sift	Benign	0.085	T;T
Sift4G	Uncertain	0.027	D;D
Polyphen		1.0	D;D
Vest4		0.11
MutPred		0.57		Loss of disorder (P = 0.0061);Loss of disorder (P = 0.0061);
MVP		0.35
MPC		0.17
ClinPred		0.71	D
GERP RS		2.3
Varity_R		0.25
gMVP		0.17

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr10-38406690; COSMIC: COSV100697441; COSMIC: COSV100697441;