chr15-48134287-A-T

Position:

• chr15-48134287-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The ENST00000341459.8(SLC24A5):​c.331A>T​(p.Thr111Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,420 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: SLC24A5 ENST00000341459.8 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

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3099164).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC24A5	NM_205850.3	c.331A>T	p.Thr111Ser	missense_variant	3/9	ENST00000341459.8	NP_995322.1
SLC24A5	XM_047432394.1	c.331A>T	p.Thr111Ser	missense_variant	3/8		XP_047288350.1
SLC24A5	XM_024449901.2	c.-9A>T		5_prime_UTR_variant	2/8		XP_024305669.2
SLC24A5	XM_047432395.1	c.-9A>T		5_prime_UTR_variant	3/9		XP_047288351.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC24A5	ENST00000341459.8	c.331A>T	p.Thr111Ser	missense_variant	3/9	1	NM_205850.3	ENSP00000341550	P1
SLC24A5	ENST00000449382.2	c.151A>T	p.Thr51Ser	missense_variant	2/8	1		ENSP00000389966
SLC24A5	ENST00000463289.1	n.91A>T		non_coding_transcript_exon_variant	2/5	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1461420 Hom.: 0 Cov.: 31 AF XY: 0.00000550 AC XY: 4 AN XY: 727028

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.0000331

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.060	T
BayesDel_noAF	Benign	-0.32
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.27	T;.
Eigen	Benign	-0.17
Eigen_PC	Benign	0.059
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.77	T;D
M_CAP	Uncertain	0.12	D
MetaRNN	Benign	0.31	T;T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	0.0	N;.
MutationTaster	Benign	1.0	N;N
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	0.91	N;N
REVEL	Benign	0.23
Sift	Uncertain	0.0040	D;D
Sift4G	Uncertain	0.0080	D;D
Polyphen		0.0	B;.
Vest4		0.21
MutPred		0.55		Gain of disorder (P = 0.0402);.;
MVP		0.69
MPC		0.062
ClinPred		0.82	D
GERP RS		5.5
Varity_R		0.16
gMVP		0.53

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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;