14-92454034-C-T

Variant names:

Variant summary

Our verdict is Likely pathogenic. The variant received 9 ACMG points: 9P and 0B. PVS1PP5

The NM_153646.4(SLC24A4):c.1015C>T(p.Arg339*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000548 in 1,460,760 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

SLC24A4
NM_153646.4 stop_gained

Scores

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 3.26

Publications

2 publications found

Variant links:

Genes affected

SLC24A4 (HGNC:10978): (solute carrier family 24 member 4) This gene encodes a sodium/potassium/calcium exchange protein. The encoded antiporter transports one calcium and one potassium ion in exchange for four sodium ions and has been implicated in amelogenesis and enamel maturation. Certain variants in this gene have been associated with skin, hair, and eye pigmentation, while other variants have been identified in people with hypomaturation-type amelogenesis imperfecta. [provided by RefSeq, Nov 2023]

SLC24A4 Gene-Disease associations (from GenCC):

amelogenesis imperfecta hypomaturation type 2A5
Inheritance: AR Classification: STRONG, MODERATE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
amelogenesis imperfecta, type 3A
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
amelogenesis imperfecta type 2
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

SLC24A4 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_pathogenic. The variant received 9 ACMG points.

PVS1

Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.

PP5

Variant 14-92454034-C-T is Pathogenic according to our data. Variant chr14-92454034-C-T is described in CliVar as Pathogenic. Clinvar id is 139657.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr14-92454034-C-T is described in CliVar as Pathogenic. Clinvar id is 139657.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr14-92454034-C-T is described in CliVar as Pathogenic. Clinvar id is 139657.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr14-92454034-C-T is described in CliVar as Pathogenic. Clinvar id is 139657.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr14-92454034-C-T is described in CliVar as Pathogenic. Clinvar id is 139657.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr14-92454034-C-T is described in CliVar as Pathogenic. Clinvar id is 139657.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr14-92454034-C-T is described in CliVar as Pathogenic. Clinvar id is 139657.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr14-92454034-C-T is described in CliVar as Pathogenic. Clinvar id is 139657.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr14-92454034-C-T is described in CliVar as Pathogenic. Clinvar id is 139657.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr14-92454034-C-T is described in CliVar as Pathogenic. Clinvar id is 139657.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC24A4	NM_153646.4 link	c.1015C>T	p.Arg339*	stop_gained	Exon 11 of 17	ENST00000532405.6	NP_705932.2	Q8NFF2-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC24A4	ENST00000532405.6 link	c.1015C>T	p.Arg339*	stop_gained	Exon 11 of 17	1	NM_153646.4	ENSP00000431840.1		Q8NFF2-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000120

AC:

AN:

249834

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000295

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:

0.00000548

AC:

AN:

1460760

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

726638

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33434

American (AMR)

AF:

0.0000224

AC:

AN:

44576

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26122

East Asian (EAS)

AF:

0.00

AC:

AN:

39608

South Asian (SAS)

AF:

0.0000465

AC:

AN:

85976

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53416

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.00000270

AC:

AN:

1111504

Other (OTH)

AF:

0.00

AC:

AN:

60360

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Amelogenesis imperfecta hypomaturation type 2A5

Pathogenic:1

Feb 07, 2013

OMIM

Significance:Pathogenic

Review Status:no assertion criteria provided

Collection Method:literature only

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Pathogenic

0.50

BayesDel_noAF

Pathogenic

0.62

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

Eigen

Pathogenic

0.82

Eigen_PC

Pathogenic

0.68

FATHMM_MKL

Uncertain

0.91

PhyloP100

3.3

Vest4

0.91

ClinPred

1.0

GERP RS

4.4

Mutation Taster

=0/200

disease causing (ClinVar)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over