16-31077304-A-T

Variant names:

• chr16-31077304-A-T
• rs749670
• NM_014699.4:c.980A>T

Variant summary

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

The NM_014699.4(ZNF646):​c.980A>T​(p.Glu327Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E327G) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZNF646 NM_014699.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.126

Genes affected

ZNF646 (HGNC:29004): (zinc finger protein 646) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription, DNA-templated. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

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=0.08496693).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF646	NM_014699.4	c.980A>T	p.Glu327Val	missense_variant	Exon 2 of 3	ENST00000300850.5	NP_055514.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF646	ENST00000300850.5	c.980A>T	p.Glu327Val	missense_variant	Exon 2 of 3	1	NM_014699.4	ENSP00000300850.5
ZNF646	ENST00000394979.2	c.980A>T	p.Glu327Val	missense_variant	Exon 1 of 1	6		ENSP00000378429.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 76

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	16
DANN	Benign	0.97
DEOGEN2	Benign	0.018	.;T
Eigen	Benign	-0.46
Eigen_PC	Benign	-0.39
FATHMM_MKL	Benign	0.21	N
LIST_S2	Benign	0.64	T;T
M_CAP	Benign	0.0087	T
MetaRNN	Benign	0.085	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.90	L;L
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-1.2	N;N
REVEL	Benign	0.092
Sift	Uncertain	0.013	D;D
Sift4G	Uncertain	0.060	T;T
Polyphen		0.20	B;.
Vest4		0.32
MutPred		0.42		Loss of glycosylation at T332 (P = 0.0809);Loss of glycosylation at T332 (P = 0.0809);
MVP		0.34
MPC		0.81
ClinPred		0.34	T
GERP RS		4.2
Varity_R		0.085
gMVP		0.69

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: rs749670; hg19: chr16-31088625;