NM_153646.4:c.241+30593C>G

Variant names:

• chr14-92356571-C-G
• rs7159431
• NM_153646.4:c.241+30593C>G

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+30593C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.175 in 152,110 control chromosomes in the GnomAD database, including 3,184 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 0.18 (3184 hom., cov: 32)
• Consequence: SLC24A4 NM_153646.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.555
• Publications: 2 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.335 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC24A4	NM_153646.4	c.241+30593C>G		intron_variant	Intron 2 of 16	ENST00000532405.6	NP_705932.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC24A4	ENST00000532405.6	c.241+30593C>G		intron_variant	Intron 2 of 16	1	NM_153646.4	ENSP00000431840.1
SLC24A4	ENST00000393265.6	c.49+30593C>G		intron_variant	Intron 2 of 16	1		ENSP00000376948.2
SLC24A4	ENST00000676001.1	c.241+30593C>G		intron_variant	Intron 3 of 17			ENSP00000502715.1
SLC24A4	ENST00000531433.5	c.241+30593C>G		intron_variant	Intron 3 of 17	2		ENSP00000433302.1

Frequencies

GnomAD3 genomes AF: 0.175 AC: 26617 AN: 151992 Hom.: 3175 Cov.: 32

Gnomad AFR AF: 0.339

Gnomad AMI AF: 0.111

Gnomad AMR AF: 0.0998

Gnomad ASJ AF: 0.114

Gnomad EAS AF: 0.148

Gnomad SAS AF: 0.129

Gnomad FIN AF: 0.187

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.101

Gnomad OTH AF: 0.160

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

GnomAD4 genome AF: 0.175 AC: 26656 AN: 152110 Hom.: 3184 Cov.: 32 AF XY: 0.176 AC XY: 13071 AN XY: 74352

African (AFR) AF: 0.339 AC: 14061 AN: 41438

American (AMR) AF: 0.0996 AC: 1523 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.114 AC: 396 AN: 3472

East Asian (EAS) AF: 0.148 AC: 764 AN: 5168

South Asian (SAS) AF: 0.129 AC: 623 AN: 4820

European-Finnish (FIN) AF: 0.187 AC: 1978 AN: 10582

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.101 AC: 6854 AN: 68024

Other (OTH) AF: 0.158 AC: 332 AN: 2102

Alfa AF: 0.146 Hom.: 280

Bravo AF: 0.177

Asia WGS AF: 0.145 AC: 507 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.5
DANN	Benign	0.72
PhyloP100		-0.56
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: rs7159431; hg19: chr14-92822915;