Variant 5-814800-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_024786.3(ZDHHC11):c.1147-5C>G variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000721 in 1,538,974 control chromosomes in the GnomAD database, including 34 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00077 ( 4 hom., cov: 33)

Exomes 𝑓: 0.00072 ( 30 hom. )

Consequence

ZDHHC11
NM_024786.3 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00003738

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.946

Variant links:

Genes affected

ZDHHC11 (HGNC:19158): (zinc finger DHHC-type containing 11) Enables signaling adaptor activity. Involved in antiviral innate immune response and positive regulation of defense response to virus by host. Located in endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]

ZDHHC11 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BP6

Variant 5-814800-G-C is Benign according to our data. Variant chr5-814800-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 2655256.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr5-814800-G-C is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.000716 (993/1387612) while in subpopulation MID AF= 0.0189 (105/5556). AF 95% confidence interval is 0.016. There are 30 homozygotes in gnomad4_exome. There are 534 alleles in male gnomad4_exome subpopulation. Median coverage is 30. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZDHHC11	NM_024786.3 linkuse as main transcript	c.1147-5C>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000283441.13

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris	UniProt
ZDHHC11	ENST00000283441.13 linkuse as main transcript	c.1147-5C>G	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	1	NM_024786.3	P1	Q9H8X9-1
ZDHHC11	ENST00000507800.1 linkuse as main transcript	c.*769-5C>G	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, NMD_transcript_variant	5
ZDHHC11	ENST00000503758.6 linkuse as main transcript	n.2849-5C>G	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant	5

Frequencies

GnomAD3 genomes

AF:

0.000760

AC:

115

AN:

151244

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000340

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00138

Gnomad ASJ

AF:

0.00462

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00188

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.000636

Gnomad OTH

AF:

0.00241

GnomAD3 exomes

AF:

0.000805

AC:

159

AN:

197598

Hom.:

AF XY:

0.000929

AC XY:

100

AN XY:

107622

show subpopulations

Gnomad AFR exome

AF:

0.000213

Gnomad AMR exome

AF:

0.00155

Gnomad ASJ exome

AF:

0.00264

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00131

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000727

Gnomad OTH exome

AF:

0.00158

GnomAD4 exome

AF:

0.000716

AC:

993

AN:

1387612

Hom.:

Cov.:

AF XY:

0.000777

AC XY:

534

AN XY:

687644

show subpopulations

Gnomad4 AFR exome

AF:

0.00149

Gnomad4 AMR exome

AF:

0.00133

Gnomad4 ASJ exome

AF:

0.00254

Gnomad4 EAS exome

AF:

0.0000815

Gnomad4 SAS exome

AF:

0.000951

Gnomad4 FIN exome

AF:

0.0000578

Gnomad4 NFE exome

AF:

0.000530

Gnomad4 OTH exome

AF:

0.00162

GnomAD4 genome

AF:

0.000766

AC:

116

AN:

151362

Hom.:

Cov.:

AF XY:

0.000662

AC XY:

AN XY:

73972

show subpopulations

Gnomad4 AFR

AF:

0.000339

Gnomad4 AMR

AF:

0.00145

Gnomad4 ASJ

AF:

0.00462

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00188

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000636

Gnomad4 OTH

AF:

0.00238

Alfa

AF:

0.00101

Hom.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Dec 01, 2022

ZDHHC11: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

1.1

DANN

Benign

0.49

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000037

dbscSNV1_RF

Benign

0.018

SpliceAI score (max)

0.17

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over