6-157647311-G-C

Variant names:

• chr6-157647311-G-C
• NM_024630.3:c.908G>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_024630.3(ZDHHC14):​c.908G>C​(p.Ser303Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZDHHC14 NM_024630.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.48
• Publications: 0 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.908G>C	p.Ser303Thr	missense	Exon 7 of 9	NP_078906.2
	ZDHHC14	NM_153746.2		c.908G>C	p.Ser303Thr	missense	Exon 7 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.908G>C	p.Ser303Thr	missense	Exon 7 of 9	ENSP00000352821.5	Q8IZN3-1
	ZDHHC14	ENST00000414563.6	TSL:1	c.908G>C	p.Ser303Thr	missense	Exon 7 of 9	ENSP00000410713.2	Q8IZN3-2
	ZDHHC14	ENST00000341375.12	TSL:1	n.559G>C		non_coding_transcript_exon	Exon 6 of 8

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

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	0.33
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.030
CADD	Pathogenic	28
DANN	Uncertain	0.99
DEOGEN2	Benign	0.12	T
Eigen	Uncertain	0.61
Eigen_PC	Uncertain	0.66
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.85	T
M_CAP	Benign	0.033	D
MetaRNN	Uncertain	0.66	D
MetaSVM	Benign	-0.87	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		9.5
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-2.4	N
REVEL	Benign	0.27
Sift	Benign	0.051	T
Sift4G	Benign	0.11	T
Polyphen		0.73	P
Vest4		0.70
MutPred		0.47		Loss of catalytic residue at S303 (P = 0.0896)
MVP		0.30
MPC		0.59
ClinPred		0.94	D
GERP RS		5.5
Varity_R		0.39
gMVP		0.85
Mutation Taster		=26/74	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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

hg19: chr6-158068343;