19-53576890-A-T

Position:

• chr19-53576890-A-T

Variant summary

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

The NM_001079906.2(ZNF331):​c.330A>T​(p.Arg110Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,868 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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: 31)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: ZNF331 NM_001079906.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.643

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 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=0.054951817).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF331	NM_001079906.2	c.330A>T	p.Arg110Ser	missense_variant	6/6	ENST00000449416.6	NP_001073375.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF331	ENST00000449416.6	c.330A>T	p.Arg110Ser	missense_variant	6/6	5	NM_001079906.2	ENSP00000393817.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1461868 Hom.: 0 Cov.: 58 AF XY: 0.00000275 AC XY: 2 AN XY: 727238

Gnomad4 AFR exome AF: 0.0000299

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.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	0.17
DANN	Benign	0.86
DEOGEN2	Benign	0.056	T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.026	N
LIST_S2	Benign	0.11	.;.;.;.;T;.;.;.;.;.;.;T;.;.;.
M_CAP	Benign	0.0011	T
MetaRNN	Benign	0.055	T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.3	L;L;L;L;L;L;L;L;L;L;.;.;L;L;L
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-0.15	.;N;.;N;N;N;N;.;N;N;N;N;.;.;.
REVEL	Benign	0.034
Sift	Benign	0.64	.;T;.;T;T;T;T;.;T;T;T;T;.;.;.
Sift4G	Benign	0.31	.;T;.;T;T;T;T;.;T;T;T;T;.;.;.
Polyphen		0.0	B;B;B;B;B;B;B;B;B;B;.;.;B;B;B
Vest4		0.072, 0.088, 0.078, 0.087, 0.075, 0.073
MutPred		0.47		Loss of MoRF binding (P = 0.015);Loss of MoRF binding (P = 0.015);Loss of MoRF binding (P = 0.015);Loss of MoRF binding (P = 0.015);Loss of MoRF binding (P = 0.015);Loss of MoRF binding (P = 0.015);Loss of MoRF binding (P = 0.015);Loss of MoRF binding (P = 0.015);Loss of MoRF binding (P = 0.015);Loss of MoRF binding (P = 0.015);Loss of MoRF binding (P = 0.015);Loss of MoRF binding (P = 0.015);Loss of MoRF binding (P = 0.015);Loss of MoRF binding (P = 0.015);Loss of MoRF binding (P = 0.015);
MVP		0.38
MPC		0.68
ClinPred		0.033	T
GERP RS		-5.3
Varity_R		0.057
gMVP		0.12

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: rs8109631; hg19: chr19-54080144;