NM_205850.3:c.534G>A

Variant names:

• chr15-48134928-G-A
• rs138902406
• NM_205850.3:c.534G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Moderate BP6 BP7

The NM_205850.3(SLC24A5):​c.534G>A​(p.Ala178Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00008 in 1,612,476 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. A178A) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.00011 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000077 (0 hom.)
• Consequence: SLC24A5 NM_205850.3 synonymous
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:2
• Conservation: PhyloP100: 0.196
• Publications: 0 publications found

Genes affected

SLC24A5 (HGNC:20611): (solute carrier family 24 member 5) This gene is a member of the potassium-dependent sodium/calcium exchanger family and encodes an intracellular membrane protein with 2 large hydrophilic loops and 2 sets of multiple transmembrane-spanning segments. Sequence variation in this gene has been associated with differences in skin pigmentation. [provided by RefSeq, Jul 2008]

MYEF2 (HGNC:17940): (myelin expression factor 2) Enables RNA binding activity. Involved in myotube differentiation and neuron differentiation. Located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BP6: Variant 15-48134928-G-A is Benign according to our data. Variant chr15-48134928-G-A is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 284318.
• BP7: Synonymous conserved (PhyloP=0.196 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_205850.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC24A5	NM_205850.3	MANE Select	c.534G>A	p.Ala178Ala	synonymous	Exon 5 of 9	NP_995322.1	Q71RS6-1
	MYEF2	NM_016132.5	MANE Select	c.*7980C>T		3_prime_UTR	Exon 17 of 17	NP_057216.3
	MYEF2	NM_001301210.2		c.*7980C>T		3_prime_UTR	Exon 16 of 16	NP_001288139.2	A0A0A0MQW0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC24A5	ENST00000341459.8	TSL:1 MANE Select	c.534G>A	p.Ala178Ala	synonymous	Exon 5 of 9	ENSP00000341550.3	Q71RS6-1
	SLC24A5	ENST00000449382.2	TSL:1	c.354G>A	p.Ala118Ala	synonymous	Exon 4 of 8	ENSP00000389966.2	Q71RS6-2
	MYEF2	ENST00000324324.12	TSL:1 MANE Select	c.*7980C>T		3_prime_UTR	Exon 17 of 17	ENSP00000316950.7	A0A0A0MR39

Frequencies

GnomAD3 genomes AF: 0.000105 AC: 16 AN: 152086 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.000577

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000717 AC: 18 AN: 250872 AF XY: 0.0000664

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.000597

Gnomad EAS exome AF: 0.000109

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000353

Gnomad OTH exome AF: 0.000164

GnomAD4 exome AF: 0.0000774 AC: 113 AN: 1460272 Hom.: 0 Cov.: 30 AF XY: 0.0000881 AC XY: 64 AN XY: 726336

African (AFR) AF: 0.000180 AC: 6 AN: 33418

American (AMR) AF: 0.0000224 AC: 1 AN: 44698

Ashkenazi Jewish (ASJ) AF: 0.000805 AC: 21 AN: 26086

East Asian (EAS) AF: 0.000101 AC: 4 AN: 39660

South Asian (SAS) AF: 0.000163 AC: 14 AN: 86002

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53382

Middle Eastern (MID) AF: 0.000521 AC: 3 AN: 5762

European-Non Finnish (NFE) AF: 0.0000513 AC: 57 AN: 1110932

Other (OTH) AF: 0.000116 AC: 7 AN: 60332

GnomAD4 genome AF: 0.000105 AC: 16 AN: 152204 Hom.: 0 Cov.: 32 AF XY: 0.000107 AC XY: 8 AN XY: 74430

African (AFR) AF: 0.0000481 AC: 2 AN: 41552

American (AMR) AF: 0.000131 AC: 2 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.000577 AC: 2 AN: 3466

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5178

South Asian (SAS) AF: 0.000622 AC: 3 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000882 AC: 6 AN: 67990

Other (OTH) AF: 0.00 AC: 0 AN: 2110

Alfa AF: 0.0000966 Hom.: 0

Bravo AF: 0.0000945

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.0000548

EpiControl AF: 0.000178

ClinVar

ClinVar submissions

Significance: Conflicting classifications of pathogenicity

Revision: criteria provided, conflicting classifications

Pathogenic	VUS	Benign	Condition
-	1	1	not provided (2)
-	-	1	SLC24A5-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	7.1
DANN	Benign	0.62
PhyloP100		0.20

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs138902406; hg19: chr15-48427125; COSMIC: COSV58317109; COSMIC: COSV58317109;