Variant 1-85657892-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_017953.4(ZNHIT6):c.1327G>A(p.Val443Met) variant causes a missense change. The variant allele was found at a frequency of 0.00000344 in 1,454,388 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

ZNHIT6
NM_017953.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.98

Variant links:

Genes affected

ZNHIT6 (HGNC:26089): (zinc finger HIT-type containing 6) Enables ATPase binding activity; TFIID-class transcription factor complex binding activity; and identical protein binding activity. Involved in box C/D snoRNP assembly; protein complex oligomerization; and snoRNA localization. Located in extracellular exosome. Part of pre-snoRNP complex. [provided by Alliance of Genome Resources, Apr 2022]

ZNHIT6 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.814

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ZNHIT6	NM_017953.4 linkuse as main transcript	c.1327G>A	p.Val443Met	missense_variant	9/10	ENST00000370574.4	NP_060423.3
ZNHIT6	NM_001170670.2 linkuse as main transcript	c.1210G>A	p.Val404Met	missense_variant	10/11		NP_001164141.1
ZNHIT6	XM_024447736.2 linkuse as main transcript	c.1248-3794G>A		intron_variant			XP_024303504.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNHIT6	ENST00000370574.4 linkuse as main transcript	c.1327G>A	p.Val443Met	missense_variant	9/10	1	NM_017953.4	ENSP00000359606	P2	Q9NWK9-1
ZNHIT6	ENST00000431532.6 linkuse as main transcript	c.1210G>A	p.Val404Met	missense_variant	10/11	2		ENSP00000414344	A2	Q9NWK9-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000344

AC:

AN:

1454388

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

723492

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

0.00000451

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

Jun 13, 2023

The c.1327G>A (p.V443M) alteration is located in exon 9 (coding exon 9) of the ZNHIT6 gene. This alteration results from a G to A substitution at nucleotide position 1327, causing the valine (V) at amino acid position 443 to be replaced by a methionine (M). 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

Pathogenic

0.77

BayesDel_addAF

Pathogenic

0.36

BayesDel_noAF

Pathogenic

0.28

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.48

.;T

Eigen

Pathogenic

0.72

Eigen_PC

Pathogenic

0.67

FATHMM_MKL

Uncertain

0.88

LIST_S2

Uncertain

0.94

D;D

M_CAP

Benign

0.069

MetaRNN

Pathogenic

0.81

D;D

MetaSVM

Uncertain

-0.16

MutationAssessor

Pathogenic

3.0

.;M

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.57

PROVEAN

Uncertain

-2.8

D;D

REVEL

Uncertain

0.48

Sift

Uncertain

0.0010

D;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

1.0

.;D

Vest4

0.83

MutPred

0.52

.;Gain of disorder (P = 0.1008);

MVP

0.86

MPC

0.69

ClinPred

0.99

GERP RS

4.8

Varity_R

0.66

gMVP

0.63

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over