rs145401990

Variant names:

• chrX-75421896-C-A
• rs145401990
• NM_144969.3:c.831G>T

Your query was ambiguous. Multiple possible variants found:

• chrX-75421896-C-A
• chrX-75421896-C-G
• chrX-75421896-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_144969.3(ZDHHC15):​c.831G>T​(p.Lys277Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000912 in 1,097,072 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in ClinVar.

• Frequency:
  • Genomes: not found (cov: 21)
  • Exomes 𝑓: 9.1e-7 (0 hom. 0 hem.)
• Consequence: ZDHHC15 NM_144969.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.265
• Publications: 2 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.03524497).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZDHHC15	NM_144969.3	c.831G>T	p.Lys277Asn	missense_variant	Exon 9 of 12	ENST00000373367.8	NP_659406.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZDHHC15	ENST00000373367.8	c.831G>T	p.Lys277Asn	missense_variant	Exon 9 of 12	1	NM_144969.3	ENSP00000362465.3
ZDHHC15	ENST00000541184.1	c.804G>T	p.Lys268Asn	missense_variant	Exon 8 of 11	2		ENSP00000445420.1

Frequencies

GnomAD3 genomes Cov.: 21

GnomAD2 exomes AF: 0.00000548 AC: 1 AN: 182384 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000368

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 9.12e-7 AC: 1 AN: 1097072 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 362764

African (AFR) AF: 0.00 AC: 0 AN: 26340

American (AMR) AF: 0.0000285 AC: 1 AN: 35081

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19328

East Asian (EAS) AF: 0.00 AC: 0 AN: 30174

South Asian (SAS) AF: 0.00 AC: 0 AN: 54038

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40508

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4124

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 841436

Other (OTH) AF: 0.00 AC: 0 AN: 46043

GnomAD4 genome Cov.: 21

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.096
BayesDel_addAF	Benign	-0.64	T
BayesDel_noAF	Benign	-1.0
CADD	Benign	13
DANN	Benign	0.97
DEOGEN2	Benign	0.068	T;.
FATHMM_MKL	Benign	0.27	N
LIST_S2	Benign	0.73	T;T
M_CAP	Benign	0.0021	T
MetaRNN	Benign	0.035	T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	-1.1	N;.
PhyloP100		-0.27
PrimateAI	Benign	0.41	T
PROVEAN	Benign	0.55	N;N
REVEL	Benign	0.057
Sift	Benign	0.55	T;T
Sift4G	Benign	0.37	T;T
Polyphen		0.0	B;.
Vest4		0.17
MutPred		0.47		Loss of methylation at K277 (P = 0.0064);.;
MVP		0.16
MPC		0.44
ClinPred		0.33	T
GERP RS		-1.8
Varity_R		0.074
gMVP		0.34
Mutation Taster		=87/13	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs145401990; hg19: chrX-74641731;