NM_001370215.1:c.838G>A

Variant names:

• chr19-56621945-G-A
• rs760589190
• NM_001370215.1:c.838G>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001370215.1(ZNF71):​c.838G>A​(p.Gly280Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000056 in 1,606,890 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 34)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: ZNF71 NM_001370215.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.68
• 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.402387).

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.838G>A	p.Gly280Ser	missense	Exon 4 of 4	NP_001357144.1	M0R0C0
	ZNF71	NM_001370214.1		c.658G>A	p.Gly220Ser	missense	Exon 3 of 3	NP_001357143.1	Q9NQZ8
	ZNF71	NM_021216.5		c.658G>A	p.Gly220Ser	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.838G>A	p.Gly280Ser	missense	Exon 4 of 4	ENSP00000471138.2	M0R0C0
	ZNF71	ENST00000328070.10	TSL:1	c.658G>A	p.Gly220Ser	missense	Exon 3 of 3	ENSP00000328245.5	Q9NQZ8
	ENSG00000293626	ENST00000716550.1		n.160+8007G>A		intron	N/A	ENSP00000520562.1	A0ABB0MV33

Frequencies

GnomAD3 genomes AF: 0.0000132 AC: 2 AN: 151988 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.00

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: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000801 AC: 2 AN: 249840 AF XY: 0.00000740

Gnomad AFR exome AF: 0.00

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: 0.0000178

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000481 AC: 7 AN: 1454902 Hom.: 0 Cov.: 33 AF XY: 0.00000276 AC XY: 2 AN XY: 724108

African (AFR) AF: 0.00 AC: 0 AN: 30030

American (AMR) AF: 0.00 AC: 0 AN: 44086

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25808

East Asian (EAS) AF: 0.00 AC: 0 AN: 39670

South Asian (SAS) AF: 0.00 AC: 0 AN: 86146

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53188

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5714

European-Non Finnish (NFE) AF: 0.00000630 AC: 7 AN: 1110654

Other (OTH) AF: 0.00 AC: 0 AN: 59606

GnomAD4 genome AF: 0.0000132 AC: 2 AN: 151988 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 74248

African (AFR) AF: 0.00 AC: 0 AN: 41368

American (AMR) AF: 0.00 AC: 0 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10602

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 67968

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.0000774 Hom.: 0

Bravo AF: 0.0000302

ExAC AF: 0.00000824 AC: 1

EpiCase AF: 0.0000545

EpiControl AF: 0.00

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	Uncertain	0.43
BayesDel_addAF	Benign	-0.088	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.098	T
Eigen	Benign	-0.078
Eigen_PC	Benign	-0.16
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.40	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	1.1	L
PhyloP100		3.7
PrimateAI	Uncertain	0.57	T
PROVEAN	Pathogenic	-5.5	D
REVEL	Benign	0.19
Sift	Uncertain	0.0020	D
Sift4G	Pathogenic	0.0010	D
Polyphen		0.71	P
Vest4		0.31
MVP		0.22
MPC		0.97
ClinPred		0.94	D
GERP RS		2.4
Varity_R		0.30
gMVP		0.073
Mutation Taster		=97/3	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: rs760589190; hg19: chr19-57133313;