chrX-75379158-T-C

Variant names:

• chrX-75379158-T-C
• rs144128364
• NM_144969.3:c.1008A>G

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_144969.3(ZDHHC15):​c.1008A>G​(p.Glu336Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0006 in 1,209,708 control chromosomes in the GnomAD database, including 1 homozygotes. There are 229 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00026 (0 hom., 6 hem., cov: 23)
  • Exomes 𝑓: 0.00064 (1 hom. 223 hem.)
• Consequence: ZDHHC15 NM_144969.3 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.20
• Publications: 1 publications found

Genes affected

ZDHHC15 (HGNC:20342): (zinc finger DHHC-type palmitoyltransferase 15) The protein encoded by this gene belongs to the DHHC palmitoyltransferase family. Mutations in this gene are associated with mental retardatio X-linked type 91 (MRX91). Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2009]

ZDHHC15 Gene-Disease associations (from GenCC):

• intellectual disability, X-linked 91

  Inheritance: XL, Unknown Classification: LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• X-linked complex neurodevelopmental disorder

  Inheritance: XL Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BP6: Variant X-75379158-T-C is Benign according to our data. Variant chrX-75379158-T-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 212628.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.2 with no splicing effect.
• BS2: High Hemizygotes in GnomAd4 at 6 XL,Unknown gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_144969.3. 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
	ZDHHC15	NM_144969.3	MANE Select	c.1008A>G	p.Glu336Glu	synonymous	Exon 11 of 12	NP_659406.1
	ZDHHC15	NM_001146256.2		c.981A>G	p.Glu327Glu	synonymous	Exon 10 of 11	NP_001139728.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZDHHC15	ENST00000373367.8	TSL:1 MANE Select	c.1008A>G	p.Glu336Glu	synonymous	Exon 11 of 12	ENSP00000362465.3
	ZDHHC15	ENST00000858993.1		c.1008A>G	p.Glu336Glu	synonymous	Exon 11 of 11	ENSP00000529052.1
	ZDHHC15	ENST00000858994.1		c.1008A>G	p.Glu336Glu	synonymous	Exon 11 of 12	ENSP00000529053.1

Frequencies

GnomAD3 genomes AF: 0.000259 AC: 29 AN: 112039 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.0000649

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000380

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00426

Gnomad NFE AF: 0.000413

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000262 AC: 48 AN: 183018 AF XY: 0.000311

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000329

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000453

Gnomad OTH exome AF: 0.000443

GnomAD4 exome AF: 0.000635 AC: 697 AN: 1097616 Hom.: 1 Cov.: 30 AF XY: 0.000614 AC XY: 223 AN XY: 363070

African (AFR) AF: 0.0000379 AC: 1 AN: 26389

American (AMR) AF: 0.000256 AC: 9 AN: 35193

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19369

East Asian (EAS) AF: 0.00 AC: 0 AN: 30191

South Asian (SAS) AF: 0.00 AC: 0 AN: 54109

European-Finnish (FIN) AF: 0.0000247 AC: 1 AN: 40515

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4131

European-Non Finnish (NFE) AF: 0.000791 AC: 666 AN: 841651

Other (OTH) AF: 0.000434 AC: 20 AN: 46068

GnomAD4 genome AF: 0.000259 AC: 29 AN: 112092 Hom.: 0 Cov.: 23 AF XY: 0.000175 AC XY: 6 AN XY: 34254

African (AFR) AF: 0.0000647 AC: 2 AN: 30906

American (AMR) AF: 0.000379 AC: 4 AN: 10542

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2651

East Asian (EAS) AF: 0.00 AC: 0 AN: 3557

South Asian (SAS) AF: 0.00 AC: 0 AN: 2664

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6133

Middle Eastern (MID) AF: 0.00467 AC: 1 AN: 214

European-Non Finnish (NFE) AF: 0.000413 AC: 22 AN: 53209

Other (OTH) AF: 0.00 AC: 0 AN: 1529

Alfa AF: 0.000564 Hom.: 5

Bravo AF: 0.000321

EpiCase AF: 0.000382

EpiControl AF: 0.000653

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	6.8
DANN	Benign	0.59
PhyloP100		1.2
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs144128364; hg19: chrX-74598993;