rs146354037

Variant names:

• chr19-56621309-A-G
• rs146354037
• NM_001370215.1:c.202A>G

Your query was ambiguous. Multiple possible variants found:

• chr19-56621309-A-G
• chr19-56621309-A-T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001370215.1(ZNF71):​c.202A>G​(p.Asn68Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000044 in 1,522,572 control chromosomes in the GnomAD database, including 2 homozygotes. 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 0.000099 (1 hom., cov: 33)
  • Exomes 𝑓: 0.000038 (1 hom.)
• Consequence: ZNF71 NM_001370215.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.278
• 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 -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.021836072).

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.202A>G	p.Asn68Asp	missense	Exon 4 of 4	NP_001357144.1	M0R0C0
	ZNF71	NM_001370214.1		c.22A>G	p.Asn8Asp	missense	Exon 3 of 3	NP_001357143.1	Q9NQZ8
	ZNF71	NM_021216.5		c.22A>G	p.Asn8Asp	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.202A>G	p.Asn68Asp	missense	Exon 4 of 4	ENSP00000471138.2	M0R0C0
	ZNF71	ENST00000328070.10	TSL:1	c.22A>G	p.Asn8Asp	missense	Exon 3 of 3	ENSP00000328245.5	Q9NQZ8
	ENSG00000293626	ENST00000716550.1		n.160+7371A>G		intron	N/A	ENSP00000520562.1	A0ABB0MV33

Frequencies

GnomAD3 genomes AF: 0.0000723 AC: 11 AN: 152094 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000242

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: 0.000478

GnomAD2 exomes AF: 0.0000554 AC: 10 AN: 180396 AF XY: 0.0000315

Gnomad AFR exome AF: 0.000588

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: 0.000243

GnomAD4 exome AF: 0.0000379 AC: 52 AN: 1370360 Hom.: 1 Cov.: 30 AF XY: 0.0000357 AC XY: 24 AN XY: 671992

African (AFR) AF: 0.000726 AC: 22 AN: 30322

American (AMR) AF: 0.00 AC: 0 AN: 29564

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20112

East Asian (EAS) AF: 0.00 AC: 0 AN: 38892

South Asian (SAS) AF: 0.0000141 AC: 1 AN: 70852

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50004

Middle Eastern (MID) AF: 0.000565 AC: 3 AN: 5314

European-Non Finnish (NFE) AF: 9.35e-7 AC: 1 AN: 1068958

Other (OTH) AF: 0.000444 AC: 25 AN: 56342

GnomAD4 genome AF: 0.0000985 AC: 15 AN: 152212 Hom.: 1 Cov.: 33 AF XY: 0.000107 AC XY: 8 AN XY: 74442

African (AFR) AF: 0.000337 AC: 14 AN: 41512

American (AMR) AF: 0.00 AC: 0 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

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

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68002

Other (OTH) AF: 0.000473 AC: 1 AN: 2114

Alfa AF: 0.0000340 Hom.: 0

Bravo AF: 0.0000793

ESP6500AA AF: 0.000454 AC: 2

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.0000415 AC: 5

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

ClinVar submissions as Germline

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	0.074
BayesDel_addAF	Benign	-0.64	T
BayesDel_noAF	Benign	-0.80
CADD	Benign	8.5
DANN	Benign	0.54
DEOGEN2	Benign	0.025	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.00065	N
LIST_S2	Benign	0.057	T
M_CAP	Benign	0.0016	T
MetaRNN	Benign	0.022	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	-0.69	N
PhyloP100		0.28
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.060	N
REVEL	Benign	0.026
Sift	Benign	0.49	T
Sift4G	Benign	0.51	T
Polyphen		0.0	B
Vest4		0.085
MVP		0.030
MPC		0.42
ClinPred		0.0066	T
GERP RS		2.4
Varity_R		0.038
gMVP		0.0099
Mutation Taster		=100/0	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: rs146354037; hg19: chr19-57132677;