19-56622020-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001370215.1(ZNF71):c.913G>C(p.Gly305Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,110 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 35)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: ZNF71 NM_001370215.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.63

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]

ZNF71-SMIM17 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18162009).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF71	NM_001370215.1	c.913G>C	p.Gly305Arg	missense_variant	4/4	ENST00000599599.7
ZNF71-SMIM17	NR_163262.1	n.339+8082G>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF71	ENST00000599599.7	c.913G>C	p.Gly305Arg	missense_variant	4/4	2	NM_001370215.1	P1
ZNF71	ENST00000328070.10	c.733G>C	p.Gly245Arg	missense_variant	3/3	1

Frequencies

GnomAD3 genomes Cov.: 35

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461110 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 726816

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000270

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 35

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 15, 2023

The c.733G>C (p.G245R) alteration is located in exon 3 (coding exon 1) of the ZNF71 gene. This alteration results from a G to C substitution at nucleotide position 733, causing the glycine (G) at amino acid position 245 to be replaced by an arginine (R). 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	0.19
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.52
Cadd	Benign	23
Dann	Uncertain	0.99
Eigen	Benign	-0.047
Eigen_PC	Benign	-0.087
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.79	T;T
M_CAP	Benign	0.0031	T
MetaRNN	Benign	0.18	T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	1.0	N
PrimateAI	Uncertain	0.64	T
Polyphen		0.99	.;D
Vest4		0.24
MutPred		0.21		.;Gain of solvent accessibility (P = 0.0674);
MVP		0.040
MPC		1.3
ClinPred		0.66	D
GERP RS		2.8
Varity_R		0.090
gMVP		0.076

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-57133388;