19-53577122-G-C

Variant names:

• chr19-53577122-G-C
• rs1416538144
• NM_001079906.2:c.562G>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.562G>C​(p.Glu188Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,882 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: ZNF331 NM_001079906.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.83

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=0.19490919).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF331	NM_001079906.2	c.562G>C	p.Glu188Gln	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.562G>C	p.Glu188Gln	missense_variant	Exon 6 of 6	5	NM_001079906.2	ENSP00000393817.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251110 Hom.: 0 AF XY: 0.00000736 AC XY: 1 AN XY: 135860

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000289

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461882 Hom.: 0 Cov.: 34 AF XY: 0.00000275 AC XY: 2 AN XY: 727236

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000224

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

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	0.17
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.077	T;T;T;T;T;T;T;T;T;T;T;T;T
Eigen	Benign	-0.33
Eigen_PC	Benign	-0.48
FATHMM_MKL	Benign	0.17	N
LIST_S2	Benign	0.15	.;.;.;.;T;.;.;.;.;.;.;.;.
M_CAP	Benign	0.0015	T
MetaRNN	Benign	0.19	T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.36	N;N;N;N;N;N;N;N;N;N;N;N;N
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-1.9	.;N;.;N;N;N;N;.;N;N;.;.;.
REVEL	Benign	0.043
Sift	Uncertain	0.026	.;D;.;D;D;D;D;.;D;D;.;.;.
Sift4G	Benign	0.063	.;T;.;T;T;T;T;.;T;T;.;.;.
Polyphen		0.95	P;P;P;P;P;P;P;P;P;P;P;P;P
Vest4		0.087, 0.14, 0.10, 0.12, 0.11
MutPred		0.36		Gain of MoRF binding (P = 0.0426);Gain of MoRF binding (P = 0.0426);Gain of MoRF binding (P = 0.0426);Gain of MoRF binding (P = 0.0426);Gain of MoRF binding (P = 0.0426);Gain of MoRF binding (P = 0.0426);Gain of MoRF binding (P = 0.0426);Gain of MoRF binding (P = 0.0426);Gain of MoRF binding (P = 0.0426);Gain of MoRF binding (P = 0.0426);Gain of MoRF binding (P = 0.0426);Gain of MoRF binding (P = 0.0426);Gain of MoRF binding (P = 0.0426);
MVP		0.39
MPC		1.6
ClinPred		0.37	T
GERP RS		2.3
Varity_R		0.10
gMVP		0.044

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: rs1416538144; hg19: chr19-54080376;