chr6-157653560-C-T

Variant names:

• chr6-157653560-C-T
• rs8180688
• NM_024630.3:c.1001C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_024630.3(ZDHHC14):​c.1001C>T​(p.Thr334Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00312 in 1,613,990 control chromosomes in the GnomAD database, including 18 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0022 (4 hom., cov: 32)
  • Exomes 𝑓: 0.0032 (14 hom.)
• Consequence: ZDHHC14 NM_024630.3 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.94
• Publications: 11 publications found

Genes affected

ZDHHC14 (HGNC:20341): (zinc finger DHHC-type palmitoyltransferase 14) Enables palmitoyltransferase activity. Involved in peptidyl-L-cysteine S-palmitoylation. Located in endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0045975447).
• BP6: Variant 6-157653560-C-T is Benign according to our data. Variant chr6-157653560-C-T is described in ClinVar as Benign. ClinVar VariationId is 3770533.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 4 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024630.3. 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
	ZDHHC14	NM_024630.3	MANE Select	c.1001C>T	p.Thr334Met	missense	Exon 8 of 9	NP_078906.2
	ZDHHC14	NM_153746.2		c.1001C>T	p.Thr334Met	missense	Exon 8 of 9	NP_714968.1	Q8IZN3-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZDHHC14	ENST00000359775.10	TSL:1 MANE Select	c.1001C>T	p.Thr334Met	missense	Exon 8 of 9	ENSP00000352821.5	Q8IZN3-1
	ZDHHC14	ENST00000414563.6	TSL:1	c.1001C>T	p.Thr334Met	missense	Exon 8 of 9	ENSP00000410713.2	Q8IZN3-2
	ZDHHC14	ENST00000341375.12	TSL:1	n.652C>T		non_coding_transcript_exon	Exon 7 of 8

Frequencies

GnomAD3 genomes AF: 0.00223 AC: 339 AN: 152194 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.00113

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000458

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.0179

Gnomad SAS AF: 0.000829

Gnomad FIN AF: 0.000659

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00254

Gnomad OTH AF: 0.00191

GnomAD2 exomes AF: 0.00281 AC: 706 AN: 251092 AF XY: 0.00263

Gnomad AFR exome AF: 0.000616

Gnomad AMR exome AF: 0.000289

Gnomad ASJ exome AF: 0.000795

Gnomad EAS exome AF: 0.0160

Gnomad FIN exome AF: 0.000326

Gnomad NFE exome AF: 0.00305

Gnomad OTH exome AF: 0.00228

GnomAD4 exome AF: 0.00321 AC: 4692 AN: 1461678 Hom.: 14 Cov.: 31 AF XY: 0.00305 AC XY: 2216 AN XY: 727150

African (AFR) AF: 0.000568 AC: 19 AN: 33480

American (AMR) AF: 0.000268 AC: 12 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.000842 AC: 22 AN: 26136

East Asian (EAS) AF: 0.0132 AC: 523 AN: 39698

South Asian (SAS) AF: 0.000672 AC: 58 AN: 86258

European-Finnish (FIN) AF: 0.000563 AC: 30 AN: 53264

Middle Eastern (MID) AF: 0.00104 AC: 6 AN: 5768

European-Non Finnish (NFE) AF: 0.00349 AC: 3883 AN: 1111962

Other (OTH) AF: 0.00230 AC: 139 AN: 60392

GnomAD4 genome AF: 0.00222 AC: 338 AN: 152312 Hom.: 4 Cov.: 32 AF XY: 0.00219 AC XY: 163 AN XY: 74484

African (AFR) AF: 0.00113 AC: 47 AN: 41566

American (AMR) AF: 0.000457 AC: 7 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00115 AC: 4 AN: 3472

East Asian (EAS) AF: 0.0179 AC: 93 AN: 5186

South Asian (SAS) AF: 0.000622 AC: 3 AN: 4820

European-Finnish (FIN) AF: 0.000659 AC: 7 AN: 10616

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

European-Non Finnish (NFE) AF: 0.00254 AC: 173 AN: 68028

Other (OTH) AF: 0.00189 AC: 4 AN: 2114

Alfa AF: 0.00284 Hom.: 5

Bravo AF: 0.00239

TwinsUK AF: 0.00458 AC: 17

ALSPAC AF: 0.00182 AC: 7

ESP6500AA AF: 0.000908 AC: 4

ESP6500EA AF: 0.00209 AC: 18

ExAC AF: 0.00272 AC: 330

Asia WGS AF: 0.00462 AC: 16 AN: 3478

EpiCase AF: 0.00333

EpiControl AF: 0.00344

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.069
BayesDel_addAF	Benign	-0.52	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0066	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-0.94
FATHMM_MKL	Benign	0.69	D
LIST_S2	Uncertain	0.90	D
MetaRNN	Benign	0.0046	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	0.81	L
PhyloP100		2.9
PrimateAI	Benign	0.48	T
PROVEAN	Benign	0.17	N
REVEL	Benign	0.13
Sift	Benign	0.15	T
Sift4G	Benign	0.13	T
Polyphen		0.052	B
Vest4		0.30
MVP		0.068
MPC		0.35
ClinPred		0.011	T
GERP RS		5.3
Varity_R		0.041
gMVP		0.60
Mutation Taster		=87/13	polymorphism

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

Other links and lift over

dbSNP: rs8180688; hg19: chr6-158074592; COSMIC: COSV100399062;