rs749670

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Uncertain significance. The variant received 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. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as (no stars).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZNF646 NM_014699.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.126
• Publications: 51 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08496693).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014699.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF646	NM_014699.4	MANE Select	c.980A>T	p.Glu327Val	missense	Exon 2 of 3	NP_055514.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF646	ENST00000300850.5	TSL:1 MANE Select	c.980A>T	p.Glu327Val	missense	Exon 2 of 3	ENSP00000300850.5	O15015-2
	ZNF646	ENST00000914100.1		c.980A>T	p.Glu327Val	missense	Exon 1 of 2	ENSP00000584159.1
	ZNF646	ENST00000394979.2	TSL:6	c.980A>T	p.Glu327Val	missense	Exon 1 of 1	ENSP00000378429.2	O15015-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 76

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
M_CAP	Benign	0.0087	T
MetaRNN	Benign	0.085	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.90	L
PhyloP100		0.13
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.092
Sift	Uncertain	0.013	D
Sift4G	Uncertain	0.060	T
Polyphen		0.20	B
Vest4		0.32
MutPred		0.42		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

Other links and lift over

dbSNP: rs749670; hg19: chr16-31088625;