14-92348113-G-A

Variant names:

• chr14-92348113-G-A
• rs12586368
• NM_153646.4:c.241+22135G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_153646.4(SLC24A4):​c.241+22135G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.133 in 152,086 control chromosomes in the GnomAD database, including 1,547 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.13 (1547 hom., cov: 32)
• Consequence: SLC24A4 NM_153646.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.03
• Publications: 3 publications found

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.192 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153646.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC24A4	NM_153646.4	MANE Select	c.241+22135G>A		intron	N/A	NP_705932.2
	SLC24A4	NM_001378620.1		c.241+22135G>A		intron	N/A	NP_001365549.1
	SLC24A4	NM_001425254.1		c.241+22135G>A		intron	N/A	NP_001412183.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC24A4	ENST00000532405.6	TSL:1 MANE Select	c.241+22135G>A		intron	N/A	ENSP00000431840.1
	SLC24A4	ENST00000393265.6	TSL:1	c.49+22135G>A		intron	N/A	ENSP00000376948.2
	SLC24A4	ENST00000676001.1		c.241+22135G>A		intron	N/A	ENSP00000502715.1

Frequencies

GnomAD3 genomes AF: 0.133 AC: 20138 AN: 151966 Hom.: 1544 Cov.: 32

Gnomad AFR AF: 0.196

Gnomad AMI AF: 0.111

Gnomad AMR AF: 0.0779

Gnomad ASJ AF: 0.110

Gnomad EAS AF: 0.147

Gnomad SAS AF: 0.127

Gnomad FIN AF: 0.186

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0991

Gnomad OTH AF: 0.133

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.133 AC: 20157 AN: 152086 Hom.: 1547 Cov.: 32 AF XY: 0.134 AC XY: 9978 AN XY: 74346

African (AFR) AF: 0.196 AC: 8114 AN: 41448

American (AMR) AF: 0.0777 AC: 1189 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.110 AC: 380 AN: 3468

East Asian (EAS) AF: 0.147 AC: 762 AN: 5176

South Asian (SAS) AF: 0.127 AC: 613 AN: 4826

European-Finnish (FIN) AF: 0.186 AC: 1961 AN: 10568

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.0991 AC: 6740 AN: 67990

Other (OTH) AF: 0.131 AC: 275 AN: 2104

Alfa AF: 0.108 Hom.: 1040

Bravo AF: 0.130

Asia WGS AF: 0.134 AC: 466 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.33
DANN	Benign	0.63
PhyloP100		-2.0
Mutation Taster		=100/0	polymorphism (auto)

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: rs12586368; hg19: chr14-92814457;