19-37243045-T-C

Variant names:

• chr19-37243045-T-C
• NM_001387601.1:c.809T>C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001387601.1(ZNF383):​c.809T>C​(p.Ile270Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,856 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: ZNF383 NM_001387601.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.216

Genes affected

ZNF383 (HGNC:18609): (zinc finger protein 383) The protein encoded by this gene is a KRAB-related zinc finger protein that inhibits the transcription of some MAPK signaling pathway genes. The repressor activity resides in the KRAB domain of the encoded protein. [provided by RefSeq, Sep 2016]

ENSG00000267605 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.043621182).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF383	NM_001387601.1	c.809T>C	p.Ile270Thr	missense_variant	Exon 6 of 6	ENST00000684119.1	NP_001374530.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF383	ENST00000684119.1	c.809T>C	p.Ile270Thr	missense_variant	Exon 6 of 6		NM_001387601.1	ENSP00000507972.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461856 Hom.: 0 Cov.: 32 AF XY: 0.00000550 AC XY: 4 AN XY: 727222

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000360

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jun 29, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.809T>C (p.I270T) alteration is located in exon 5 (coding exon 4) of the ZNF383 gene. This alteration results from a T to C substitution at nucleotide position 809, causing the isoleucine (I) at amino acid position 270 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	0.062
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	17
DANN	Benign	0.68
DEOGEN2	Benign	0.015	T;T;T
Eigen	Benign	-0.96
Eigen_PC	Benign	-0.86
FATHMM_MKL	Benign	0.028	N
LIST_S2	Benign	0.078	.;.;T
M_CAP	Benign	0.0031	T
MetaRNN	Benign	0.044	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.47	N;N;N
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	1.3	.;.;N
REVEL	Benign	0.057
Sift	Benign	1.0	.;.;T
Sift4G	Benign	0.90	T;T;T
Polyphen		0.041	B;B;B
Vest4		0.35
MutPred		0.42		Loss of stability (P = 0.001);Loss of stability (P = 0.001);Loss of stability (P = 0.001);
MVP		0.20
MPC		0.44
ClinPred		0.081	T
GERP RS		0.55
Varity_R		0.031
gMVP		0.032

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: chr19-37733947;