Variant 11-65116921-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_014205.4(ZNHIT2):c.733C>T(p.Leu245Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000346 in 1,444,678 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 0.0000035 ( 0 hom. )

Consequence

ZNHIT2
NM_014205.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.52

Variant links:

Genes affected

ZNHIT2 (HGNC:1177): (zinc finger HIT-type containing 2) Predicted to enable metal ion binding activity. [provided by Alliance of Genome Resources, Apr 2022]

ZNHIT2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.30425054).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNHIT2	NM_014205.4 linkuse as main transcript	c.733C>T	p.Leu245Phe	missense_variant	1/1	ENST00000310597.6	NP_055020.1	Q9UHR6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNHIT2	ENST00000310597.6 linkuse as main transcript	c.733C>T	p.Leu245Phe	missense_variant	1/1	6	NM_014205.4	ENSP00000308548.4		Q9UHR6
ZNHIT2	ENST00000528598.1 linkuse as main transcript	c.238C>T	p.Leu80Phe	missense_variant	2/2	3		ENSP00000436896.1		E9PQB8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000431

AC:

AN:

232224

Hom.:

AF XY:

0.00

AC XY:

AN XY:

127226

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000296

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:

0.00000346

AC:

AN:

1444678

Hom.:

Cov.:

AF XY:

0.00000278

AC XY:

AN XY:

718342

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000226

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000762

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.02e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Dec 27, 2022

The c.733C>T (p.L245F) alteration is located in exon 1 (coding exon 1) of the ZNHIT2 gene. This alteration results from a C to T substitution at nucleotide position 733, causing the leucine (L) at amino acid position 245 to be replaced by a phenylalanine (F). 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

0.23

BayesDel_addAF

Uncertain

0.041

BayesDel_noAF

Benign

-0.18

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.35

T;T

Eigen

Uncertain

0.41

Eigen_PC

Uncertain

0.40

FATHMM_MKL

Benign

0.49

LIST_S2

Benign

0.60

T;T

M_CAP

Benign

0.024

MetaRNN

Benign

0.30

T;T

MetaSVM

Benign

-0.84

MutationAssessor

Uncertain

2.4

M;.

MutationTaster

Benign

0.99

PrimateAI

Pathogenic

0.80

PROVEAN

Uncertain

-2.7

D;N

REVEL

Benign

0.14

Sift

Benign

0.12

T;T

Sift4G

Pathogenic

0.0

D;.

Polyphen

1.0

D;.

Vest4

0.58

MutPred

0.33

Gain of glycosylation at S248 (P = 0.2704);.;

MVP

0.43

MPC

1.5

ClinPred

0.96

GERP RS

4.7

Varity_R

0.17

gMVP

0.56

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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