rs146590296

Variant names:

• chr19-37242478-C-G
• NM_001387601.1:c.242C>G

Your query was ambiguous. Multiple possible variants found:

• chr19-37242478-C-G
• chr19-37242478-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001387601.1(ZNF383):​c.242C>G​(p.Ser81Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000704 in 1,420,366 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S81L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: ZNF383 NM_001387601.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0730

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19982591).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF383	NM_001387601.1	c.242C>G	p.Ser81Trp	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.242C>G	p.Ser81Trp	missense_variant	Exon 6 of 6		NM_001387601.1	ENSP00000507972.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.04e-7 AC: 1 AN: 1420366 Hom.: 0 Cov.: 27 AF XY: 0.00000142 AC XY: 1 AN XY: 703478

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: 9.22e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.086	T
BayesDel_noAF	Benign	-0.36
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.21	T;T;T;.
Eigen	Uncertain	0.26
Eigen_PC	Benign	0.14
FATHMM_MKL	Benign	0.18	N
LIST_S2	Benign	0.74	.;.;T;D
M_CAP	Benign	0.0028	T
MetaRNN	Benign	0.20	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.5	M;M;M;.
PrimateAI	Uncertain	0.50	T
PROVEAN	Uncertain	-4.3	.;.;D;.
REVEL	Benign	0.080
Sift	Uncertain	0.0030	.;.;D;.
Sift4G	Uncertain	0.036	D;D;D;D
Polyphen		1.0	D;D;D;.
Vest4		0.53
MutPred		0.36		Loss of disorder (P = 0.0014);Loss of disorder (P = 0.0014);Loss of disorder (P = 0.0014);Loss of disorder (P = 0.0014);
MVP		0.63
MPC		0.82
ClinPred		0.96	D
GERP RS		2.9
Varity_R		0.28
gMVP		0.16

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: chr19-37733380;