rs1426654

Variant names:

• chr15-48134287-A-C
• rs1426654
• NM_205850.3:c.331A>C

Your query was ambiguous. Multiple possible variants found:

• chr15-48134287-A-C
• chr15-48134287-A-G
• chr15-48134287-A-T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_205850.3(SLC24A5):​c.331A>C​(p.Thr111Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T111A) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC24A5 NM_205850.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.57

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.375359).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC24A5	NM_205850.3	c.331A>C	p.Thr111Pro	missense_variant	Exon 3 of 9	ENST00000341459.8	NP_995322.1
SLC24A5	XM_047432394.1	c.331A>C	p.Thr111Pro	missense_variant	Exon 3 of 8		XP_047288350.1
SLC24A5	XM_024449901.2	c.-9A>C		5_prime_UTR_variant	Exon 2 of 8		XP_024305669.2
SLC24A5	XM_047432395.1	c.-9A>C		5_prime_UTR_variant	Exon 3 of 9		XP_047288351.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC24A5	ENST00000341459.8	c.331A>C	p.Thr111Pro	missense_variant	Exon 3 of 9	1	NM_205850.3	ENSP00000341550.3
SLC24A5	ENST00000449382.2	c.151A>C	p.Thr51Pro	missense_variant	Exon 2 of 8	1		ENSP00000389966.2
SLC24A5	ENST00000463289.1	n.91A>C		non_coding_transcript_exon_variant	Exon 2 of 5	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.70
BayesDel_addAF	Benign	-0.028	T
BayesDel_noAF	Benign	-0.28
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.57	D;.
Eigen	Benign	-0.17
Eigen_PC	Benign	0.060
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.77	T;D
M_CAP	Uncertain	0.15	D
MetaRNN	Benign	0.38	T;T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	0.0	N;.
PrimateAI	Pathogenic	0.83	D
PROVEAN	Benign	-0.98	N;N
REVEL	Benign	0.25
Sift	Uncertain	0.0020	D;D
Sift4G	Uncertain	0.0040	D;D
Polyphen		0.0050	B;.
Vest4		0.28
MutPred		0.55		Loss of glycosylation at T111 (P = 0.0566);.;
MVP		0.74
MPC		0.091
ClinPred		0.93	D
GERP RS		5.5
Varity_R		0.75
gMVP		0.93
Mutation Taster		=77/23	polymorphism

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

Publications

LitVar

Other links and lift over

dbSNP: rs1426654; hg19: chr15-48426484;