chr19-53576856-A-C

Variant names:

• chr19-53576856-A-C
• rs1387980508
• NM_001079906.2:c.296A>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.296A>C​(p.Tyr99Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,886 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: 6.8e-7 (0 hom.)
• Consequence: ZNF331 NM_001079906.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.352

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=0.150929).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF331	NM_001079906.2	c.296A>C	p.Tyr99Ser	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.296A>C	p.Tyr99Ser	missense_variant	Exon 6 of 6	5	NM_001079906.2	ENSP00000393817.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461886 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 727242

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	6.9
DANN	Benign	0.52
DEOGEN2	Benign	0.095	T;T;T;T;T;.;T;T;T;T;T;.;T;T;T;T;T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.066	N
LIST_S2	Benign	0.17	.;.;.;.;T;T;.;.;.;.;.;T;.;T;.;.;.
M_CAP	Benign	0.0016	T
MetaRNN	Benign	0.084	T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	1.8	L;L;L;L;L;.;L;L;L;L;L;.;.;.;L;L;L
PrimateAI	Benign	0.28	T
PROVEAN	Uncertain	-3.1	.;D;.;D;D;N;D;D;.;D;D;D;D;D;.;.;.
REVEL	Benign	0.026
Sift	Benign	0.27	.;T;.;T;T;D;T;T;.;T;T;T;T;T;.;.;.
Sift4G	Benign	0.34	.;T;.;T;T;D;T;T;.;T;T;T;T;T;.;.;.
Polyphen		0.0010	B;B;B;B;B;.;B;B;B;B;B;.;.;.;B;B;B
Vest4		0.14, 0.16, 0.14, 0.14, 0.16
MutPred		0.38		Gain of disorder (P = 0.0189);Gain of disorder (P = 0.0189);Gain of disorder (P = 0.0189);Gain of disorder (P = 0.0189);Gain of disorder (P = 0.0189);Gain of disorder (P = 0.0189);Gain of disorder (P = 0.0189);Gain of disorder (P = 0.0189);Gain of disorder (P = 0.0189);Gain of disorder (P = 0.0189);Gain of disorder (P = 0.0189);Gain of disorder (P = 0.0189);Gain of disorder (P = 0.0189);Gain of disorder (P = 0.0189);Gain of disorder (P = 0.0189);Gain of disorder (P = 0.0189);Gain of disorder (P = 0.0189);
MVP		0.18
MPC		0.86
ClinPred		0.11	T
GERP RS		-0.26
Varity_R		0.14
gMVP		0.18

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

LitVar

Other links and lift over

dbSNP: rs1387980508; hg19: chr19-54080110;