19-56621588-G-A

Variant names:

• chr19-56621588-G-A
• rs753057359
• NM_001370215.1:c.481G>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001370215.1(ZNF71):​c.481G>A​(p.Ala161Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000103 in 1,461,850 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.000010 (0 hom.)
• Consequence: ZNF71 NM_001370215.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.84

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]

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

ZNF71-SMIM17 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.049091548).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF71	NM_001370215.1	c.481G>A	p.Ala161Thr	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.481G>A	p.Ala161Thr	missense_variant	Exon 4 of 4	2	NM_001370215.1	ENSP00000471138.2
ZNF71	ENST00000328070.10	c.301G>A	p.Ala101Thr	missense_variant	Exon 3 of 3	1		ENSP00000328245.5
ZIM2-AS1	ENST00000650950.1	n.201+19997G>A		intron_variant	Intron 2 of 5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.0000159 AC: 4 AN: 251120 Hom.: 0 AF XY: 0.0000221 AC XY: 3 AN XY: 135764

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 SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000352

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000103 AC: 15 AN: 1461850 Hom.: 0 Cov.: 31 AF XY: 0.0000124 AC XY: 9 AN XY: 727224

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000126

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000308 Hom.: 0

Bravo AF: 0.00000378

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.066
BayesDel_addAF	Benign	-0.47	T
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.020
DANN	Benign	0.67
DEOGEN2	Benign	0.019	.;T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.0026	N
LIST_S2	Benign	0.13	T;T
M_CAP	Benign	0.00068	T
MetaRNN	Benign	0.049	T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.41	.;N
PrimateAI	Benign	0.20	T
PROVEAN	Benign	0.16	.;N
REVEL	Benign	0.014
Sift	Benign	0.44	.;T
Sift4G	Benign	0.092	.;T
Polyphen		0.0010	.;B
Vest4		0.018
MutPred		0.16		.;Gain of glycosylation at A101 (P = 0.0026);
MVP		0.014
MPC		0.36
ClinPred		0.032	T
GERP RS		-6.2
Varity_R		0.019
gMVP		0.012

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

Publications

LitVar

Other links and lift over

dbSNP: rs753057359; hg19: chr19-57132956;