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14-92323938-G-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BS1BS2

The NM_153646.4(SLC24A4):c.108G>T(p.Ala36=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00114 in 1,611,392 control chromosomes in the GnomAD database, including 19 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Synonymous variant affecting the same amino acid position (i.e. A36A) has been classified as Benign.

Frequency

Genomes: 𝑓 0.0063 ( 9 hom., cov: 32)
Exomes 𝑓: 0.00061 ( 10 hom. )

Consequence

SLC24A4
NM_153646.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.281
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 -13 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=-0.38).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 14-92323938-G-T is Benign according to our data. Variant chr14-92323938-G-T is described in ClinVar as [Benign]. Clinvar id is 768675.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=-0.281 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00625 (952/152276) while in subpopulation AFR AF= 0.0219 (910/41558). AF 95% confidence interval is 0.0207. There are 9 homozygotes in gnomad4. There are 428 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 9 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SLC24A4NM_153646.4 linkuse as main transcriptc.108G>T p.Ala36= synonymous_variant 1/17 ENST00000532405.6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SLC24A4ENST00000532405.6 linkuse as main transcriptc.108G>T p.Ala36= synonymous_variant 1/171 NM_153646.4 A1Q8NFF2-1
SLC24A4ENST00000393265.6 linkuse as main transcriptc.-63+1303G>T intron_variant 1 Q8NFF2-2
SLC24A4ENST00000676001.1 linkuse as main transcriptc.108G>T p.Ala36= synonymous_variant 2/18 A1Q8NFF2-1
SLC24A4ENST00000531433.5 linkuse as main transcriptc.108G>T p.Ala36= synonymous_variant 2/182 P4Q8NFF2-3

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00623
AC:
948
AN:
152158
Hom.:
9
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0219
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00177
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000193
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.0000882
Gnomad OTH
AF:
0.00335
GnomAD3 exomes
AF:
0.00160
AC:
392
AN:
245152
Hom.:
5
AF XY:
0.00117
AC XY:
155
AN XY:
133026
show subpopulations
Gnomad AFR exome
AF:
0.0226
Gnomad AMR exome
AF:
0.000584
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000658
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000542
Gnomad OTH exome
AF:
0.000667
GnomAD4 exome
AF:
0.000605
AC:
883
AN:
1459116
Hom.:
10
Cov.:
31
AF XY:
0.000537
AC XY:
390
AN XY:
725934
show subpopulations
Gnomad4 AFR exome
AF:
0.0220
Gnomad4 AMR exome
AF:
0.000784
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.0000697
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000135
Gnomad4 OTH exome
AF:
0.00148
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00625
AC:
952
AN:
152276
Hom.:
9
Cov.:
32
AF XY:
0.00575
AC XY:
428
AN XY:
74456
show subpopulations
Gnomad4 AFR
AF:
0.0219
Gnomad4 AMR
AF:
0.00176
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000194
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000882
Gnomad4 OTH
AF:
0.00331
Alfa
AF:
0.000266
Hom.:
0
Bravo
AF:
0.00720
EpiCase
AF:
0.000109
EpiControl
AF:
0.00

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 testingInvitaeDec 31, 2019- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.38
Cadd
Benign
9.9
Dann
Benign
0.91

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.030
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: rs149248445; hg19: chr14-92790282; API