Variant 14-73921092-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000555044.6(ZNF410):c.1116G>T(p.Glu372Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000335 in 1,614,066 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00017 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000019 ( 0 hom. )

Consequence

ZNF410
ENST00000555044.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.43

Variant links:

Genes affected

ZNF410 (HGNC:20144): (zinc finger protein 410) Enables sequence-specific double-stranded 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]

ZNF410 links:

ENSG00000258653 (HGNC:):

ENSG00000258653 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.054507583).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF410	NM_021188.3 linkuse as main transcript	c.1116G>T	p.Glu372Asp	missense_variant	9/12	ENST00000555044.6	NP_067011.1	Q86VK4-1A0A024R691Q53FM1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ZNF410	ENST00000555044.6 linkuse as main transcript	c.1116G>T	p.Glu372Asp	missense_variant	9/12	1	NM_021188.3	ENSP00000451763.2	Q86VK4-1
ENSG00000258653	ENST00000556551.2 linkuse as main transcript	n.*1375G>T		non_coding_transcript_exon_variant	18/22	2		ENSP00000451484.1	G3V3Y1
ENSG00000258653	ENST00000556551.2 linkuse as main transcript	n.*1375G>T		3_prime_UTR_variant	18/22	2		ENSP00000451484.1	G3V3Y1

Frequencies

GnomAD3 genomes

AF:

0.000164

AC:

AN:

152202

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000603

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:

0.00

GnomAD3 exomes

AF:

0.0000438

AC:

AN:

251274

Hom.:

AF XY:

0.0000295

AC XY:

AN XY:

135812

show subpopulations

Gnomad AFR exome

AF:

0.000615

Gnomad AMR exome

AF:

0.0000289

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000192

AC:

AN:

1461746

Hom.:

Cov.:

AF XY:

0.0000206

AC XY:

AN XY:

727182

show subpopulations

Gnomad4 AFR exome

AF:

0.000687

Gnomad4 AMR exome

AF:

0.0000447

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:

0.00

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

AF:

0.000171

AC:

AN:

152320

Hom.:

Cov.:

AF XY:

0.000228

AC XY:

AN XY:

74486

show subpopulations

Gnomad4 AFR

AF:

0.000626

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000214

Hom.:

Bravo

AF:

0.000200

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000494

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 03, 2024

The c.1167G>T (p.E389D) alteration is located in exon 10 (coding exon 9) of the ZNF410 gene. This alteration results from a G to T substitution at nucleotide position 1167, causing the glutamic acid (E) at amino acid position 389 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

0.11

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Benign

0.91

DEOGEN2

Benign

0.030

.;.;.;T;.;.;.;T

Eigen

Benign

-0.12

Eigen_PC

Benign

-0.019

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.74

T;T;.;T;T;T;T;T

M_CAP

Benign

0.0046

MetaRNN

Benign

0.055

T;T;T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.34

.;N;.;N;.;.;.;.

MutationTaster

Benign

0.86

N;N;N;N;N

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-0.26

N;N;N;N;N;.;.;N

REVEL

Benign

0.10

Sift

Benign

0.085

T;T;T;T;T;.;.;D

Sift4G

Benign

0.42

T;T;T;T;T;T;.;T

Polyphen

0.34, 0.14

.;B;.;B;.;.;.;.

Vest4

0.26

MutPred

0.20

.;Loss of phosphorylation at S370 (P = 0.1751);.;Loss of phosphorylation at S370 (P = 0.1751);.;.;.;.;

MVP

0.17

MPC

0.38

ClinPred

0.043

GERP RS

3.2

Varity_R

0.042

gMVP

0.20

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over