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GeneBe

10-112438345-A-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BS1BS2

The NM_022494.3(ZDHHC6):c.726T>C(p.Ile242=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00136 in 1,353,784 control chromosomes in the GnomAD database, including 24 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0076 ( 13 hom., cov: 32)
Exomes 𝑓: 0.00057 ( 11 hom. )

Consequence

ZDHHC6
NM_022494.3 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.51
Variant links:
Genes affected
ZDHHC6 (HGNC:19160): (zinc finger DHHC-type palmitoyltransferase 6) Enables palmitoyltransferase activity. Involved in positive regulation of mitochondrial fusion and protein palmitoylation. Located in endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.35).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 10-112438345-A-G is Benign according to our data. Variant chr10-112438345-A-G is described in ClinVar as [Benign]. Clinvar id is 778473.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=1.51 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00758 (1155/152312) while in subpopulation AFR AF= 0.0262 (1090/41572). AF 95% confidence interval is 0.0249. There are 13 homozygotes in gnomad4. There are 563 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 13 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ZDHHC6NM_022494.3 linkuse as main transcriptc.726T>C p.Ile242= synonymous_variant 6/11 ENST00000369405.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ZDHHC6ENST00000369405.7 linkuse as main transcriptc.726T>C p.Ile242= synonymous_variant 6/111 NM_022494.3 P4Q9H6R6-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00755
AC:
1149
AN:
152194
Hom.:
13
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0262
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00321
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:
0.0000147
Gnomad OTH
AF:
0.00718
GnomAD3 exomes
AF:
0.00106
AC:
111
AN:
104946
Hom.:
1
AF XY:
0.000706
AC XY:
40
AN XY:
56634
show subpopulations
Gnomad AFR exome
AF:
0.0191
Gnomad AMR exome
AF:
0.000545
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000427
Gnomad OTH exome
AF:
0.000724
GnomAD4 exome
AF:
0.000568
AC:
682
AN:
1201472
Hom.:
11
Cov.:
26
AF XY:
0.000495
AC XY:
291
AN XY:
587984
show subpopulations
Gnomad4 AFR exome
AF:
0.0226
Gnomad4 AMR exome
AF:
0.000704
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000119
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000158
Gnomad4 OTH exome
AF:
0.00150
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00758
AC:
1155
AN:
152312
Hom.:
13
Cov.:
32
AF XY:
0.00756
AC XY:
563
AN XY:
74488
show subpopulations
Gnomad4 AFR
AF:
0.0262
Gnomad4 AMR
AF:
0.00320
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00710
Alfa
AF:
0.00396
Hom.:
6
Bravo
AF:
0.00886
Asia WGS
AF:
0.000577
AC:
2
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeDec 04, 2017- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.35
Cadd
Benign
8.2
Dann
Benign
0.83
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.030
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.

Other links and lift over

dbSNP: rs34823410; hg19: chr10-114198103; API