19-53571625-G-T

Variant names:

• chr19-53571625-G-T
• rs377282635
• NM_001079906.2:c.31G>T

Variant summary

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

The NM_001079906.2(ZNF331):​c.31G>T​(p.Val11Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZNF331 NM_001079906.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.80

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF331	NM_001079906.2	c.31G>T	p.Val11Leu	missense_variant	Exon 5 of 6	ENST00000449416.6	NP_001073375.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF331	ENST00000449416.6	c.31G>T	p.Val11Leu	missense_variant	Exon 5 of 6	5	NM_001079906.2	ENSP00000393817.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.71
BayesDel_addAF	Benign	-0.0075	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.14	T;T;T;.;T;T;.;T;T;.;.;T;T;T;.;T;T;.;T;.;T;T;T
Eigen	Uncertain	0.55
Eigen_PC	Uncertain	0.39
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.83	.;.;.;T;.;T;T;.;.;.;T;.;.;.;T;.;T;T;.;T;.;.;T
M_CAP	Benign	0.0030	T
MetaRNN	Uncertain	0.52	D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D
MetaSVM	Benign	-1.0	T
MutationAssessor	Pathogenic	2.9	M;M;M;.;M;M;.;M;M;.;.;M;M;M;.;.;.;.;M;.;M;M;.
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	-2.2	.;N;.;D;N;N;D;N;N;D;D;.;N;N;N;D;N;D;.;D;.;D;D
REVEL	Benign	0.18
Sift	Uncertain	0.022	.;D;.;D;D;D;D;D;D;D;D;.;D;D;D;D;D;D;.;D;.;D;D
Sift4G	Uncertain	0.011	.;D;.;D;D;D;D;D;D;D;D;.;D;D;D;D;D;D;.;D;.;D;D
Polyphen		1.0	D;D;D;.;D;D;.;D;D;.;.;D;D;D;.;.;.;.;D;.;D;D;.
Vest4		0.53, 0.55, 0.55, 0.50, 0.51, 0.52
MutPred		0.65		Gain of sheet (P = 0.0149);Gain of sheet (P = 0.0149);Gain of sheet (P = 0.0149);Gain of sheet (P = 0.0149);Gain of sheet (P = 0.0149);Gain of sheet (P = 0.0149);Gain of sheet (P = 0.0149);Gain of sheet (P = 0.0149);Gain of sheet (P = 0.0149);Gain of sheet (P = 0.0149);Gain of sheet (P = 0.0149);Gain of sheet (P = 0.0149);Gain of sheet (P = 0.0149);Gain of sheet (P = 0.0149);Gain of sheet (P = 0.0149);Gain of sheet (P = 0.0149);Gain of sheet (P = 0.0149);Gain of sheet (P = 0.0149);Gain of sheet (P = 0.0149);Gain of sheet (P = 0.0149);Gain of sheet (P = 0.0149);Gain of sheet (P = 0.0149);Gain of sheet (P = 0.0149);
MVP		0.69
MPC		1.5
ClinPred		0.82	D
GERP RS		4.1
Varity_R		0.22
gMVP		0.55

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs377282635; hg19: chr19-54074879;