chr10-97452265-C-T

Variant names:

• chr10-97452265-C-T
• rs529320386
• NM_198046.3:c.419C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_198046.3(ZDHHC16):​c.419C>T​(p.Pro140Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000427 in 1,614,142 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: 𝑓 0.000026 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000044 (0 hom.)
• Consequence: ZDHHC16 NM_198046.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.75
• Publications: 3 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.111733526).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198046.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZDHHC16	NM_198046.3	MANE Select	c.419C>T	p.Pro140Leu	missense	Exon 4 of 12	NP_932163.1	Q969W1-1
	ZDHHC16	NM_032327.4		c.419C>T	p.Pro140Leu	missense	Exon 3 of 11	NP_115703.2
	ZDHHC16	NM_198043.3		c.419C>T	p.Pro140Leu	missense	Exon 3 of 10	NP_932160.1	Q969W1-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZDHHC16	ENST00000393760.6	TSL:1 MANE Select	c.419C>T	p.Pro140Leu	missense	Exon 4 of 12	ENSP00000377357.1	Q969W1-1
	ZDHHC16	ENST00000370854.7	TSL:1	c.419C>T	p.Pro140Leu	missense	Exon 3 of 11	ENSP00000359891.3	Q969W1-1
	ZDHHC16	ENST00000352634.8	TSL:1	c.419C>T	p.Pro140Leu	missense	Exon 3 of 10	ENSP00000345383.4	Q969W1-2

Frequencies

GnomAD3 genomes AF: 0.0000263 AC: 4 AN: 152190 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000835 AC: 21 AN: 251388 AF XY: 0.000118

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000867

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000264

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000445 AC: 65 AN: 1461834 Hom.: 0 Cov.: 33 AF XY: 0.0000578 AC XY: 42 AN XY: 727220

African (AFR) AF: 0.0000597 AC: 2 AN: 33480

American (AMR) AF: 0.0000894 AC: 4 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.000325 AC: 28 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53364

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5768

European-Non Finnish (NFE) AF: 0.0000252 AC: 28 AN: 1112010

Other (OTH) AF: 0.0000331 AC: 2 AN: 60394

GnomAD4 genome AF: 0.0000263 AC: 4 AN: 152308 Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2 AN XY: 74462

African (AFR) AF: 0.0000240 AC: 1 AN: 41580

American (AMR) AF: 0.00 AC: 0 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.000621 AC: 3 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68010

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.0000299 Hom.: 0

Bravo AF: 0.0000302

ExAC AF: 0.0000906 AC: 11

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.18
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.27	T
Eigen	Uncertain	0.27
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Benign	0.73	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.044	D
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-0.60	T
MutationAssessor	Benign	1.8	L
PhyloP100		4.7
PrimateAI	Uncertain	0.56	T
PROVEAN	Uncertain	-3.8	D
REVEL	Benign	0.084
Sift	Uncertain	0.0010	D
Sift4G	Benign	0.11	T
Polyphen		0.014	B
Vest4		0.53
MutPred		0.44		Loss of disorder (P = 0.0059)
MVP		0.77
MPC		0.29
ClinPred		0.15	T
GERP RS		5.5
PromoterAI		0.017	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.23
gMVP		0.80
Mutation Taster		=78/22	polymorphism

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

Other links and lift over

dbSNP: rs529320386; hg19: chr10-99212022; COSMIC: COSV61748741; COSMIC: COSV61748741;