chr5-748498-A-G

Position:

• chr5-748498-A-G

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_001351303.2(ZDHHC11B):​c.690T>C​(p.Thr230Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00099 in 1,363,106 control chromosomes in the GnomAD database, including 300 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00093 (21 hom., cov: 25)
  • Exomes 𝑓: 0.0010 (279 hom.)
• Consequence: ZDHHC11B NM_001351303.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.41

Genes affected

ZDHHC11B (HGNC:32962): (zinc finger DHHC-type containing 11B) Predicted to enable protein-cysteine S-palmitoyltransferase activity. Predicted to be involved in several processes, including antiviral innate immune response; peptidyl-L-cysteine S-palmitoylation; and positive regulation of defense response to virus by host. Predicted to be located in endosome membrane. Predicted to be active in Golgi apparatus and endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BP6: Variant 5-748498-A-G is Benign according to our data. Variant chr5-748498-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2655254.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-2.41 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 21 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZDHHC11B	NM_001351303.2	c.690T>C	p.Thr230Thr	synonymous_variant	8/14	ENST00000508859.8	NP_001338232.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZDHHC11B	ENST00000508859.8	c.690T>C	p.Thr230Thr	synonymous_variant	8/14	5	NM_001351303.2	ENSP00000442373.2
ZDHHC11B	ENST00000522356.3	n.*691T>C		non_coding_transcript_exon_variant	9/16	2		ENSP00000505988.1
ZDHHC11B	ENST00000622126.2	n.156T>C		non_coding_transcript_exon_variant	2/2	5
ZDHHC11B	ENST00000522356.3	n.*691T>C		3_prime_UTR_variant	9/16	2		ENSP00000505988.1

Frequencies

GnomAD3 genomes AF: 0.000926 AC: 119 AN: 128528 Hom.: 21 Cov.: 25

Gnomad AFR AF: 0.000812

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000903

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00128

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000232

Gnomad MID AF: 0.0108

Gnomad NFE AF: 0.00114

Gnomad OTH AF: 0.00114

GnomAD3 exomes AF: 0.000860 AC: 172 AN: 199896 Hom.: 43 AF XY: 0.00104 AC XY: 112 AN XY: 108080

Gnomad AFR exome AF: 0.000190

Gnomad AMR exome AF: 0.000468

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00123

Gnomad SAS exome AF: 0.00110

Gnomad FIN exome AF: 0.000117

Gnomad NFE exome AF: 0.00114

Gnomad OTH exome AF: 0.00137

GnomAD4 exome AF: 0.000996 AC: 1230 AN: 1234478 Hom.: 279 Cov.: 32 AF XY: 0.00101 AC XY: 617 AN XY: 610602

Gnomad4 AFR exome AF: 0.000765

Gnomad4 AMR exome AF: 0.000552

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000697

Gnomad4 SAS exome AF: 0.00122

Gnomad4 FIN exome AF: 0.000228

Gnomad4 NFE exome AF: 0.00103

Gnomad4 OTH exome AF: 0.00135

GnomAD4 genome AF: 0.000933 AC: 120 AN: 128628 Hom.: 21 Cov.: 25 AF XY: 0.000806 AC XY: 50 AN XY: 62070

Gnomad4 AFR AF: 0.000835

Gnomad4 AMR AF: 0.000903

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00128

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000232

Gnomad4 NFE AF: 0.00114

Gnomad4 OTH AF: 0.00114

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Feb 01, 2023

ZDHHC11B: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.7
DANN	Benign	0.34

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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

Other links and lift over

dbSNP: rs189921796; hg19: chr5-748613;