chr15-48134888-C-G

Variant summary

Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate

The NM_205850.3(SLC24A5):​c.494C>G​(p.Ser165Ter) variant causes a stop gained change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: not found (cov: 32)

Consequence

SLC24A5
NM_205850.3 stop_gained

Scores

5
1
1

Clinical Significance

Pathogenic criteria provided, single submitter P:1

Conservation

PhyloP100: 6.42
Variant links:
Genes affected
SLC24A5 (HGNC:20611): (solute carrier family 24 member 5) This gene is a member of the potassium-dependent sodium/calcium exchanger family and encodes an intracellular membrane protein with 2 large hydrophilic loops and 2 sets of multiple transmembrane-spanning segments. Sequence variation in this gene has been associated with differences in skin pigmentation. [provided by RefSeq, Jul 2008]
MYEF2 (HGNC:17940): (myelin expression factor 2) Enables RNA binding activity. Involved in myotube differentiation and neuron differentiation. Located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Pathogenic. Variant got 12 ACMG points.

PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 15-48134888-C-G is Pathogenic according to our data. Variant chr15-48134888-C-G is described in ClinVar as [Pathogenic]. Clinvar id is 2431038.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SLC24A5NM_205850.3 linkuse as main transcriptc.494C>G p.Ser165Ter stop_gained 5/9 ENST00000341459.8
MYEF2NM_016132.5 linkuse as main transcriptc.*8020G>C 3_prime_UTR_variant 17/17 ENST00000324324.12

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SLC24A5ENST00000341459.8 linkuse as main transcriptc.494C>G p.Ser165Ter stop_gained 5/91 NM_205850.3 P1Q71RS6-1
SLC24A5ENST00000449382.2 linkuse as main transcriptc.314C>G p.Ser105Ter stop_gained 4/81 Q71RS6-2
MYEF2ENST00000324324.12 linkuse as main transcriptc.*8020G>C 3_prime_UTR_variant 17/171 NM_016132.5 P4
SLC24A5ENST00000463289.1 linkuse as main transcriptn.254C>G non_coding_transcript_exon_variant 4/53

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
32

ClinVar

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

Submissions by phenotype

Oculocutaneous albinism type 6 Pathogenic:1
Pathogenic, criteria provided, single submitterclinical testingPediatrics Genetics, Post Graduate Institute of Medical Education and ResearchMar 01, 2023PVS1: null variant (nonsense, frameshift, canonical +- 2 splice sites, initiation codon, single or multiexon deletion) in a gene where LOF is a known mechanism of disease PM2: Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium PP3: Multiple lines of computational evidence support a deleterious effect on the gene or gene product (conservation, evolutionary, splicing impact, etc.) -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
0.63
D
BayesDel_noAF
Pathogenic
0.66
CADD
Pathogenic
36
DANN
Uncertain
0.99
Eigen
Pathogenic
0.92
Eigen_PC
Pathogenic
0.79
FATHMM_MKL
Pathogenic
0.99
D
MutationTaster
Benign
1.0
A;A
Vest4
0.93
GERP RS
5.3

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr15-48427085; API