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GeneBe

14-92325911-G-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_153646.4(SLC24A4):c.174G>A(p.Thr58=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.989 in 1,612,866 control chromosomes in the GnomAD database, including 790,738 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.94 ( 68466 hom., cov: 32)
Exomes 𝑓: 0.99 ( 722272 hom. )

Consequence

SLC24A4
NM_153646.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.64
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 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=-0.73).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 14-92325911-G-A is Benign according to our data. Variant chr14-92325911-G-A is described in ClinVar as [Benign]. Clinvar id is 1277530.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=-1.64 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.993 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SLC24A4NM_153646.4 linkuse as main transcriptc.174G>A p.Thr58= synonymous_variant 2/17 ENST00000532405.6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SLC24A4ENST00000532405.6 linkuse as main transcriptc.174G>A p.Thr58= synonymous_variant 2/171 NM_153646.4 A1Q8NFF2-1
SLC24A4ENST00000393265.6 linkuse as main transcriptc.-19G>A 5_prime_UTR_variant 2/171 Q8NFF2-2
SLC24A4ENST00000676001.1 linkuse as main transcriptc.174G>A p.Thr58= synonymous_variant 3/18 A1Q8NFF2-1
SLC24A4ENST00000531433.5 linkuse as main transcriptc.174G>A p.Thr58= synonymous_variant 3/182 P4Q8NFF2-3

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.944
AC:
143723
AN:
152210
Hom.:
68420
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.807
Gnomad AMI
AF:
1.00
Gnomad AMR
AF:
0.978
Gnomad ASJ
AF:
0.998
Gnomad EAS
AF:
1.00
Gnomad SAS
AF:
0.999
Gnomad FIN
AF:
1.00
Gnomad MID
AF:
0.987
Gnomad NFE
AF:
0.999
Gnomad OTH
AF:
0.959
GnomAD3 exomes
AF:
0.985
AC:
245837
AN:
249466
Hom.:
121396
AF XY:
0.989
AC XY:
133348
AN XY:
134778
show subpopulations
Gnomad AFR exome
AF:
0.804
Gnomad AMR exome
AF:
0.990
Gnomad ASJ exome
AF:
0.998
Gnomad EAS exome
AF:
1.00
Gnomad SAS exome
AF:
1.00
Gnomad FIN exome
AF:
1.00
Gnomad NFE exome
AF:
0.999
Gnomad OTH exome
AF:
0.990
GnomAD4 exome
AF:
0.994
AC:
1451835
AN:
1460538
Hom.:
722272
Cov.:
42
AF XY:
0.995
AC XY:
722643
AN XY:
726404
show subpopulations
Gnomad4 AFR exome
AF:
0.799
Gnomad4 AMR exome
AF:
0.988
Gnomad4 ASJ exome
AF:
0.999
Gnomad4 EAS exome
AF:
1.00
Gnomad4 SAS exome
AF:
1.00
Gnomad4 FIN exome
AF:
1.00
Gnomad4 NFE exome
AF:
1.00
Gnomad4 OTH exome
AF:
0.986
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.944
AC:
143826
AN:
152328
Hom.:
68466
Cov.:
32
AF XY:
0.946
AC XY:
70496
AN XY:
74486
show subpopulations
Gnomad4 AFR
AF:
0.807
Gnomad4 AMR
AF:
0.978
Gnomad4 ASJ
AF:
0.998
Gnomad4 EAS
AF:
1.00
Gnomad4 SAS
AF:
0.999
Gnomad4 FIN
AF:
1.00
Gnomad4 NFE
AF:
0.999
Gnomad4 OTH
AF:
0.959
Alfa
AF:
0.973
Hom.:
43833
Bravo
AF:
0.936
Asia WGS
AF:
0.986
AC:
3429
AN:
3478
EpiCase
AF:
0.999
EpiControl
AF:
0.999

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 testingGeneDxJun 09, 2021- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.73
Cadd
Benign
0.61
Dann
Benign
0.83

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs941646; hg19: chr14-92792255; API