chr10-97451724-C-T

Variant names:

• chr10-97451724-C-T
• rs376949987
• NM_198046.3:c.49C>T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_198046.3(ZDHHC16):​c.49C>T​(p.Arg17Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000134 in 1,613,210 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R17G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000046 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00014 (0 hom.)
• Consequence: ZDHHC16 NM_198046.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.20
• Publications: 1 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 -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.26756293).

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.49C>T	p.Arg17Cys	missense	Exon 3 of 12	NP_932163.1	Q969W1-1
	ZDHHC16	NM_032327.4		c.49C>T	p.Arg17Cys	missense	Exon 2 of 11	NP_115703.2
	ZDHHC16	NM_198043.3		c.49C>T	p.Arg17Cys	missense	Exon 2 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.49C>T	p.Arg17Cys	missense	Exon 3 of 12	ENSP00000377357.1	Q969W1-1
	ZDHHC16	ENST00000370854.7	TSL:1	c.49C>T	p.Arg17Cys	missense	Exon 2 of 11	ENSP00000359891.3	Q969W1-1
	ZDHHC16	ENST00000352634.8	TSL:1	c.49C>T	p.Arg17Cys	missense	Exon 2 of 10	ENSP00000345383.4	Q969W1-2

Frequencies

GnomAD3 genomes AF: 0.0000460 AC: 7 AN: 152258 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000482

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000685 AC: 17 AN: 248228 AF XY: 0.0000891

Gnomad AFR exome AF: 0.0000629

Gnomad AMR exome AF: 0.0000579

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000109

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000990

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000143 AC: 209 AN: 1460952 Hom.: 0 Cov.: 33 AF XY: 0.000150 AC XY: 109 AN XY: 726800

African (AFR) AF: 0.0000897 AC: 3 AN: 33456

American (AMR) AF: 0.0000447 AC: 2 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.000101 AC: 4 AN: 39700

South Asian (SAS) AF: 0.0000812 AC: 7 AN: 86208

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53280

Middle Eastern (MID) AF: 0.000193 AC: 1 AN: 5168

European-Non Finnish (NFE) AF: 0.000168 AC: 187 AN: 1111978

Other (OTH) AF: 0.0000829 AC: 5 AN: 60318

GnomAD4 genome AF: 0.0000460 AC: 7 AN: 152258 Hom.: 0 Cov.: 33 AF XY: 0.0000403 AC XY: 3 AN XY: 74396

African (AFR) AF: 0.0000482 AC: 2 AN: 41472

American (AMR) AF: 0.00 AC: 0 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5198

South Asian (SAS) AF: 0.00 AC: 0 AN: 4838

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 68048

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000642

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.0000659 AC: 8

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00

EpiControl AF: 0.000119

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	Uncertain	0.45
BayesDel_addAF	Benign	-0.092	T
BayesDel_noAF	Benign	-0.14
CADD	Pathogenic	27
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.11	T
Eigen	Uncertain	0.43
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Benign	0.68	D
LIST_S2	Uncertain	0.97	D
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.27	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		2.2
PrimateAI	Pathogenic	0.91	D
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.19
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.025	D
Polyphen		0.95	P
Vest4		0.56
MVP		0.54
MPC		0.79
ClinPred		0.19	T
GERP RS		5.6
PromoterAI		-0.16	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.6
Varity_R		0.27
gMVP		0.76
Mutation Taster		=63/37	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		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: rs376949987; hg19: chr10-99211481; COSMIC: COSV61749173; COSMIC: COSV61749173;