chr19-56621309-A-G

Variant names:

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

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).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF71	NM_001370215.1	c.202A>G	p.Asn68Asp	missense_variant	Exon 4 of 4	ENST00000599599.7	NP_001357144.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF71	ENST00000599599.7	c.202A>G	p.Asn68Asp	missense_variant	Exon 4 of 4	2	NM_001370215.1	ENSP00000471138.2
ENSG00000293626	ENST00000716550.1	n.160+7371A>G		intron_variant	Intron 3 of 5			ENSP00000520562.1

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

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 20, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.22A>G (p.N8D) alteration is located in exon 3 (coding exon 1) of the ZNF71 gene. This alteration results from a A to G substitution at nucleotide position 22, causing the asparagine (N) at amino acid position 8 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

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;T
M_CAP	Benign	0.0016	T
MetaRNN	Benign	0.022	T;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;