Variant 10-97452127-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_198046.3(ZDHHC16):c.281T>C(p.Ile94Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000273 in 1,613,928 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000028 ( 0 hom. )

Consequence

ZDHHC16
NM_198046.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.93

Variant links:

Genes affected

ZDHHC16 (HGNC:20714): (zinc finger DHHC-type palmitoyltransferase 16) Enables palmitoyltransferase activity. Involved in protein palmitoylation. Predicted to be located in endoplasmic reticulum membrane. Predicted to be integral component of membrane. Predicted to be active in Golgi apparatus. [provided by Alliance of Genome Resources, Apr 2022]

ZDHHC16 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.24649116).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZDHHC16	NM_198046.3 link	c.281T>C	p.Ile94Thr	missense_variant	4/12	ENST00000393760.6	NP_932163.1	Q969W1-1B4DNL2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZDHHC16	ENST00000393760.6 link	c.281T>C	p.Ile94Thr	missense_variant	4/12	1	NM_198046.3	ENSP00000377357.1		Q969W1-1

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.0000398

AC:

AN:

251360

Hom.:

AF XY:

0.0000662

AC XY:

AN XY:

135872

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000280

AC:

AN:

1461746

Hom.:

Cov.:

AF XY:

0.0000413

AC XY:

AN XY:

727198

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:

0.000464

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152182

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74346

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000479

Bravo

AF:

0.00000378

ExAC

AF:

0.0000412

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

Aug 12, 2024

The c.281T>C (p.I94T) alteration is located in exon 4 (coding exon 2) of the ZDHHC16 gene. This alteration results from a T to C substitution at nucleotide position 281, causing the isoleucine (I) at amino acid position 94 to be replaced by a threonine (T). 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

0.73

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.25

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.26

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

Eigen

Uncertain

0.27

Eigen_PC

Uncertain

0.39

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.96

D;.;D;D;.;D;D

M_CAP

Benign

0.018

MetaRNN

Benign

0.25

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

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.3

M;M;.;.;M;M;M

PrimateAI

Uncertain

0.60

PROVEAN

Uncertain

-3.4

D;D;D;D;D;D;D

REVEL

Benign

0.17

Sift

Benign

0.063

T;T;D;D;T;T;T

Sift4G

Uncertain

0.0030

D;D;D;D;D;D;D

Polyphen

0.047

B;B;.;P;P;B;P

Vest4

0.67

MutPred

0.49

Gain of glycosylation at I94 (P = 0.0484);Gain of glycosylation at I94 (P = 0.0484);Gain of glycosylation at I94 (P = 0.0484);Gain of glycosylation at I94 (P = 0.0484);Gain of glycosylation at I94 (P = 0.0484);Gain of glycosylation at I94 (P = 0.0484);Gain of glycosylation at I94 (P = 0.0484);

MVP

0.62

MPC

0.41

ClinPred

0.33

GERP RS

5.5

Varity_R

0.31

gMVP

0.73

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