Genetic Variant ZNHIT3:p.Asp71Asp (chr17-36493933-T-C) – ACMG Classification: Benign (-17 pts)

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_004773.4(ZNHIT3):c.213T>C(p.Asp71Asp) 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 (★★).

Frequency

Genomes: 𝑓 0.00021 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00023 ( 3 hom. )

Consequence

ZNHIT3
NM_004773.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -3.78

Publications

0 publications found

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]

ZNHIT3 Gene-Disease associations (from GenCC):

PEHO syndrome
Inheritance: AR, AD Classification: MODERATE, SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics
Mayer-Rokitansky-Kuster-Hauser syndrome
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ZNHIT3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -17 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 VariationId is 726269.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-3.78 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 3 AD,AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004773.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZNHIT3	NM_004773.4	MANE Select	c.213T>C	p.Asp71Asp	synonymous	Exon 4 of 5	NP_004764.1	Q15649-1
ZNHIT3	NM_001281432.2		c.213T>C	p.Asp71Asp	synonymous	Exon 4 of 5	NP_001268361.1	Q15649-2
ZNHIT3	NM_001281434.2		c.119-1290T>C		intron	N/A	NP_001268363.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZNHIT3	ENST00000617429.5	TSL:1 MANE Select	c.213T>C	p.Asp71Asp	synonymous	Exon 4 of 5	ENSP00000484687.1	Q15649-1
ZNHIT3	ENST00000619730.4	TSL:1	c.-127T>C		5_prime_UTR	Exon 3 of 4	ENSP00000481499.1	A0A087WY42
ZNHIT3	ENST00000612728.4	TSL:1	n.203T>C		non_coding_transcript_exon	Exon 3 of 4

Frequencies

GnomAD3 genomes

AF:

0.000210

AC:

AN:

152206

Hom.:

Cov.:

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

GnomAD2 exomes

AF:

0.000530

AC:

133

AN:

250998

AF XY:

0.000501

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 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.:

Cov.:

AF XY:

0.000223

AC XY:

162

AN XY:

726698

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33450

American (AMR)

AF:

0.0000224

AC:

AN:

44658

Ashkenazi Jewish (ASJ)

AF:

0.00888

AC:

232

AN:

26118

East Asian (EAS)

AF:

0.00

AC:

AN:

39692

South Asian (SAS)

AF:

0.0000232

AC:

AN:

86096

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53358

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.0000477

AC:

AN:

1111130

Other (OTH)

AF:

0.000862

AC:

AN:

60354

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000210

AC:

AN:

152206

Hom.:

Cov.:

AF XY:

0.000242

AC XY:

AN XY:

74360

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41446

American (AMR)

AF:

0.0000654

AC:

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00692

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5196

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.0000942

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000882

AC:

AN:

68040

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00108

Hom.:

Bravo

AF:

0.000261

EpiCase

AF:

0.000164

EpiControl

AF:

0.0000593

ClinVar

ClinVar submissions as Germline

Significance:Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.15

(source)

DANN

Benign

0.61

PhyloP100

-3.8

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over