14-92326260-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_153646.4(SLC24A4):c.241+282C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.182 in 74,120 control chromosomes in the GnomAD database, including 651 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.18 (651 hom., cov: 34)
• Consequence: SLC24A4 NM_153646.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.672

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 14-92326260-C-T is Benign according to our data. Variant chr14-92326260-C-T is described in ClinVar as [Benign]. Clinvar id is 1276946.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.23 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC24A4	NM_153646.4	c.241+282C>T		intron_variant		ENST00000532405.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC24A4	ENST00000532405.6	c.241+282C>T		intron_variant		1	NM_153646.4	A1
SLC24A4	ENST00000393265.6	c.49+282C>T		intron_variant		1
SLC24A4	ENST00000531433.5	c.241+282C>T		intron_variant		2		P4
SLC24A4	ENST00000676001.1	c.241+282C>T		intron_variant				A1

Frequencies

GnomAD3 genomes AF: 0.182 AC: 13469 AN: 74030 Hom.: 649 Cov.: 34

Gnomad AFR AF: 0.147

Gnomad AMI AF: 0.0892

Gnomad AMR AF: 0.196

Gnomad ASJ AF: 0.122

Gnomad EAS AF: 0.0609

Gnomad SAS AF: 0.248

Gnomad FIN AF: 0.221

Gnomad MID AF: 0.119

Gnomad NFE AF: 0.207

Gnomad OTH AF: 0.230

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

GnomAD4 genome AF: 0.182 AC: 13480 AN: 74120 Hom.: 651 Cov.: 34 AF XY: 0.183 AC XY: 6396 AN XY: 34960

Gnomad4 AFR AF: 0.147

Gnomad4 AMR AF: 0.195

Gnomad4 ASJ AF: 0.122

Gnomad4 EAS AF: 0.0609

Gnomad4 SAS AF: 0.252

Gnomad4 FIN AF: 0.221

Gnomad4 NFE AF: 0.206

Gnomad4 OTH AF: 0.226

Alfa AF: 0.0959 Hom.: 126

Bravo AF: 0.0860

Asia WGS AF: 0.0510 AC: 175 AN: 3468

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 19, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	6.7
Dann	Benign	0.74

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

LitVar

Other links and lift over

dbSNP: rs79363863; hg19: chr14-92792604;