NM_001370215.1:c.535A>G

Variant names:

• chr19-56621642-A-G
• rs896350281
• NM_001370215.1:c.535A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001370215.1(ZNF71):​c.535A>G​(p.Lys179Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000372 in 1,614,074 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 34)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: ZNF71 NM_001370215.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.738
• Publications: 0 publications found

Genes affected

ZNF71 (HGNC:13141): (zinc finger protein 71) Predicted to enable DNA-binding transcription activator 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 by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000293626 (HGNC:):

ZIM2-AS1 (HGNC:51304): (ZIM2 antisense RNA 1)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.058936298).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001370215.1. 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
	ZNF71	NM_001370215.1	MANE Select	c.535A>G	p.Lys179Glu	missense	Exon 4 of 4	NP_001357144.1	M0R0C0
	ZNF71	NM_001370214.1		c.355A>G	p.Lys119Glu	missense	Exon 3 of 3	NP_001357143.1	Q9NQZ8
	ZNF71	NM_021216.5		c.355A>G	p.Lys119Glu	missense	Exon 3 of 3	NP_067039.1	Q9NQZ8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF71	ENST00000599599.7	TSL:2 MANE Select	c.535A>G	p.Lys179Glu	missense	Exon 4 of 4	ENSP00000471138.2	M0R0C0
	ZNF71	ENST00000328070.10	TSL:1	c.355A>G	p.Lys119Glu	missense	Exon 3 of 3	ENSP00000328245.5	Q9NQZ8
	ENSG00000293626	ENST00000716550.1		n.160+7704A>G		intron	N/A	ENSP00000520562.1	A0ABB0MV33

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152232 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.0000241

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

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1461842 Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2 AN XY: 727222

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53382

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000450 AC: 5 AN: 1112004

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152232 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 74380

African (AFR) AF: 0.0000241 AC: 1 AN: 41458

American (AMR) AF: 0.00 AC: 0 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68036

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.088
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.78
CADD	Benign	3.1
DANN	Benign	0.42
DEOGEN2	Benign	0.036	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.017	N
LIST_S2	Benign	0.080	T
M_CAP	Benign	0.0013	T
MetaRNN	Benign	0.059	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	0.84	L
PhyloP100		-0.74
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.72	N
REVEL	Benign	0.0030
Sift	Benign	0.48	T
Sift4G	Benign	0.67	T
Polyphen		0.0	B
Vest4		0.040
MutPred		0.29		Loss of ubiquitination at K119 (P = 0.0047)
MVP		0.014
MPC		0.52
ClinPred		0.016	T
GERP RS		-4.1
Varity_R		0.044
gMVP		0.016
Mutation Taster		=99/1	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: rs896350281; hg19: chr19-57133010;