rs749670

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr16-31077304-A-C
• chr16-31077304-A-G
• chr16-31077304-A-T

Variant summary

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

The NM_014699.4(ZNF646):​c.980A>C​(p.Glu327Ala) 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 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=0.06732082).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF646	NM_014699.4	c.980A>C	p.Glu327Ala	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>C	p.Glu327Ala	missense_variant	Exon 2 of 3	1	NM_014699.4	ENSP00000300850.5
ZNF646	ENST00000394979.2	c.980A>C	p.Glu327Ala	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	0.14
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	15
DANN	Benign	0.96
DEOGEN2	Benign	0.018	.;T
Eigen	Benign	-0.60
Eigen_PC	Benign	-0.49
FATHMM_MKL	Benign	0.33	N
LIST_S2	Benign	0.70	T;T
M_CAP	Benign	0.0069	T
MetaRNN	Benign	0.067	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.90	L;L
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.71	N;N
REVEL	Benign	0.12
Sift	Benign	0.058	T;T
Sift4G	Benign	0.33	T;T
Polyphen		0.019	B;.
Vest4		0.18
MutPred		0.41		Loss of glycosylation at T332 (P = 0.0941);Loss of glycosylation at T332 (P = 0.0941);
MVP		0.30
MPC		0.73
ClinPred		0.20	T
GERP RS		4.2
Varity_R		0.044
gMVP		0.64

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-31088625;