19-53577934-G-C

Variant names:

• chr19-53577934-G-C
• rs61741983
• NM_001079906.2:c.1374G>C

Variant summary

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

The NM_001079906.2(ZNF331):​c.1374G>C​(p.Gln458His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,424 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ZNF331 NM_001079906.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.683

Genes affected

ZNF331 (HGNC:15489): (zinc finger protein 331) This gene encodes a zinc finger protein containing a KRAB (Kruppel-associated box) domain found in transcriptional repressors. This gene may be methylated and silenced in cancer cells. This gene is located within a differentially methylated region (DMR) and shows allele-specific expression in placenta. Alternative splicing and the use of alternative promoters results in multiple transcript variants encoding the same protein. [provided by RefSeq, Nov 2015]

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=0.16013631).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF331	NM_001079906.2	c.1374G>C	p.Gln458His	missense_variant	Exon 6 of 6	ENST00000449416.6	NP_001073375.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF331	ENST00000449416.6	c.1374G>C	p.Gln458His	missense_variant	Exon 6 of 6	5	NM_001079906.2	ENSP00000393817.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000407 AC: 1 AN: 245894 Hom.: 0 AF XY: 0.00000750 AC XY: 1 AN XY: 133300

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000914

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460424 Hom.: 0 Cov.: 34 AF XY: 0.00000138 AC XY: 1 AN XY: 726330

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: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	12
DANN	Benign	0.95
DEOGEN2	Benign	0.27	T;T;T;T;T;T;T;T;T;T;T;T;T
Eigen	Benign	-0.44
Eigen_PC	Benign	-0.51
FATHMM_MKL	Benign	0.32	N
LIST_S2	Benign	0.38	.;.;.;.;T;.;.;.;.;.;.;.;.
M_CAP	Benign	0.0033	T
MetaRNN	Benign	0.16	T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.1	M;M;M;M;M;M;M;M;M;M;M;M;M
PrimateAI	Benign	0.29	T
PROVEAN	Uncertain	-2.4	.;N;.;N;N;N;N;.;N;N;.;.;.
REVEL	Benign	0.063
Sift	Uncertain	0.017	.;D;.;D;D;D;D;.;D;D;.;.;.
Sift4G	Uncertain	0.055	.;T;.;T;T;T;T;.;T;T;.;.;.
Polyphen		0.30	B;B;B;B;B;B;B;B;B;B;B;B;B
Vest4		0.13, 0.18, 0.15, 0.17, 0.13, 0.14, 0.13
MutPred		0.47		Gain of methylation at R455 (P = 0.0485);Gain of methylation at R455 (P = 0.0485);Gain of methylation at R455 (P = 0.0485);Gain of methylation at R455 (P = 0.0485);Gain of methylation at R455 (P = 0.0485);Gain of methylation at R455 (P = 0.0485);Gain of methylation at R455 (P = 0.0485);Gain of methylation at R455 (P = 0.0485);Gain of methylation at R455 (P = 0.0485);Gain of methylation at R455 (P = 0.0485);Gain of methylation at R455 (P = 0.0485);Gain of methylation at R455 (P = 0.0485);Gain of methylation at R455 (P = 0.0485);
MVP		0.43
MPC		0.62
ClinPred		0.16	T
GERP RS		3.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.19
gMVP		0.040

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: rs61741983; hg19: chr19-54081188; COSMIC: COSV53476425; COSMIC: COSV53476425;