19-56621357-G-C

Variant names:

• chr19-56621357-G-C
• rs765132480
• NM_001370215.1:c.250G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001370215.1(ZNF71):​c.250G>C​(p.Gly84Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZNF71 NM_001370215.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.484
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07871303).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF71	NM_001370215.1	c.250G>C	p.Gly84Arg	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.250G>C	p.Gly84Arg	missense_variant	Exon 4 of 4	2	NM_001370215.1	ENSP00000471138.2
ENSG00000293626	ENST00000716550.1	n.160+7419G>C		intron_variant	Intron 3 of 5			ENSP00000520562.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	9.7
DANN	Benign	0.35
DEOGEN2	Benign	0.023	.;T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.043	N
LIST_S2	Benign	0.36	T;T
M_CAP	Benign	0.0016	T
MetaRNN	Benign	0.079	T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.81	.;L
PhyloP100		0.48
PrimateAI	Benign	0.30	T
PROVEAN	Benign	0.19	.;N
REVEL	Benign	0.029
Sift	Benign	0.46	.;T
Sift4G	Benign	0.72	.;T
Polyphen		0.0010	.;B
Vest4		0.12
MutPred		0.44		.;Gain of MoRF binding (P = 0.0055);
MVP		0.014
MPC		0.44
ClinPred		0.042	T
GERP RS		0.94
Varity_R		0.041
gMVP		0.015
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: rs765132480; hg19: chr19-57132725;