rs149738181

Variant names:

• chr22-23744242-C-A
• rs149738181
• NM_021916.4:c.899G>T

Your query was ambiguous. Multiple possible variants found:

• chr22-23744242-C-A
• chr22-23744242-C-G
• chr22-23744242-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_021916.4(ZNF70):​c.899G>T​(p.Arg300Leu) 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. 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. R300Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000069 (0 hom., cov: 33)
  • Failed GnomAD Quality Control
• Consequence: ZNF70 NM_021916.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.738
• Publications: 2 publications found

Genes affected

ZNF70 (HGNC:13140): (zinc finger protein 70) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II transcription regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. 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=0.21747476).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021916.4. 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
	ZNF70	NM_021916.4	MANE Select	c.899G>T	p.Arg300Leu	missense	Exon 2 of 2	NP_068735.1	Q9UC06

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF70	ENST00000341976.5	TSL:1 MANE Select	c.899G>T	p.Arg300Leu	missense	Exon 2 of 2	ENSP00000339314.3	Q9UC06
	ZNF70	ENST00000871908.1		c.899G>T	p.Arg300Leu	missense	Exon 2 of 2	ENSP00000541967.1
	ZNF70	ENST00000871909.1		c.899G>T	p.Arg300Leu	missense	Exon 3 of 3	ENSP00000541968.1

Frequencies

GnomAD3 genomes AF: 0.00000686 AC: 1 AN: 145790 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000254

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251438 AF XY: 0.00

Gnomad AFR exome AF: 0.0000615

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 34

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000685 AC: 1 AN: 145930 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 71354

African (AFR) AF: 0.0000253 AC: 1 AN: 39494

American (AMR) AF: 0.00 AC: 0 AN: 14688

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3366

East Asian (EAS) AF: 0.00 AC: 0 AN: 4740

South Asian (SAS) AF: 0.00 AC: 0 AN: 4516

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10234

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 238

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 65788

Other (OTH) AF: 0.00 AC: 0 AN: 2004

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.51
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.28	T
Eigen	Benign	0.12
Eigen_PC	Benign	0.026
FATHMM_MKL	Benign	0.54	D
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	L
PhyloP100		0.74
PrimateAI	Uncertain	0.78	T
PROVEAN	Pathogenic	-6.2	D
REVEL	Benign	0.087
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.0050	D
Polyphen		0.97	D
Vest4		0.41
MutPred		0.62		Loss of MoRF binding (P = 0.0234)
MVP		0.092
MPC		0.65
ClinPred		0.85	D
GERP RS		3.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.45
gMVP		0.11
Mutation Taster		=98/2	polymorphism

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: rs149738181; hg19: chr22-24086429;