chr17-36493933-T-C

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_004773.4(ZNHIT3):ā€‹c.213T>Cā€‹(p.Asp71=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000231 in 1,612,828 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā˜…).

Frequency

Genomes: š‘“ 0.00021 ( 0 hom., cov: 33)
Exomes š‘“: 0.00023 ( 3 hom. )

Consequence

ZNHIT3
NM_004773.4 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.78
Variant links:
Genes affected
ZNHIT3 (HGNC:12309): (zinc finger HIT-type containing 3) Predicted to enable thyroid hormone receptor binding activity. Predicted to be involved in box C/D snoRNP assembly; maturation of LSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA); and snoRNA localization. Located in cytoplasm and nucleus. Implicated in PEHO syndrome. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.88).
BP6
Variant 17-36493933-T-C is Benign according to our data. Variant chr17-36493933-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 726269.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=-3.78 with no splicing effect.
BS2
High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ZNHIT3NM_004773.4 linkuse as main transcriptc.213T>C p.Asp71= synonymous_variant 4/5 ENST00000617429.5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ZNHIT3ENST00000617429.5 linkuse as main transcriptc.213T>C p.Asp71= synonymous_variant 4/51 NM_004773.4 P1Q15649-1

Frequencies

GnomAD3 genomes
AF:
0.000210
AC:
32
AN:
152206
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000654
Gnomad ASJ
AF:
0.00692
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.0000942
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000882
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000530
AC:
133
AN:
250998
Hom.:
1
AF XY:
0.000501
AC XY:
68
AN XY:
135638
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000290
Gnomad ASJ exome
AF:
0.0111
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.0000925
Gnomad NFE exome
AF:
0.000123
Gnomad OTH exome
AF:
0.000652
GnomAD4 exome
AF:
0.000233
AC:
340
AN:
1460622
Hom.:
3
Cov.:
29
AF XY:
0.000223
AC XY:
162
AN XY:
726698
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00888
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000232
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000477
Gnomad4 OTH exome
AF:
0.000862
GnomAD4 genome
AF:
0.000210
AC:
32
AN:
152206
Hom.:
0
Cov.:
33
AF XY:
0.000242
AC XY:
18
AN XY:
74360
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000654
Gnomad4 ASJ
AF:
0.00692
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.0000942
Gnomad4 NFE
AF:
0.0000882
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.00108
Hom.:
2
Bravo
AF:
0.000261
EpiCase
AF:
0.000164
EpiControl
AF:
0.0000593

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpDec 31, 2019- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.88
CADD
Benign
0.15
DANN
Benign
0.61

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.

Other links and lift over

dbSNP: rs147606592; hg19: chr17-34849777; API