NM_001370215.1:c.545T>C

Variant names:

• chr19-56621652-T-C
• NM_001370215.1:c.545T>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The NM_001370215.1(ZNF71):​c.545T>C​(p.Met182Thr) 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. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 34)
• Consequence: ZNF71 NM_001370215.1 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.03
• 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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.084037095).
• BP6: Variant 19-56621652-T-C is Benign according to our data. Variant chr19-56621652-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 3822598.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF71	NM_001370215.1	c.545T>C	p.Met182Thr	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.545T>C	p.Met182Thr	missense_variant	Exon 4 of 4	2	NM_001370215.1	ENSP00000471138.2
ENSG00000293626	ENST00000716550.1	n.160+7714T>C		intron_variant	Intron 3 of 5			ENSP00000520562.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 34

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Jan 02, 2025

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.083
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.033
DANN	Benign	0.25
DEOGEN2	Benign	0.021	.;T
Eigen	Benign	-1.9
Eigen_PC	Benign	-2.0
FATHMM_MKL	Benign	0.0086	N
LIST_S2	Benign	0.0032	T;T
M_CAP	Benign	0.0016	T
MetaRNN	Benign	0.084	T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.085	.;N
PhyloP100		-1.0
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-0.19	.;N
REVEL	Benign	0.011
Sift	Benign	0.048	.;D
Sift4G	Uncertain	0.026	.;D
Polyphen		0.0020	.;B
Vest4		0.031
MutPred		0.36		.;Loss of catalytic residue at M122 (P = 1e-04);
MVP		0.014
MPC		0.42
ClinPred		0.049	T
GERP RS		-7.1
Varity_R		0.059
gMVP		0.032
Mutation Taster		=98/2	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

hg19: chr19-57133020;