chrX-154488194-C-T

Variant names:

• chrX-154488194-C-T
• rs782584318
• NM_019848.5:c.747G>A

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_019848.5(SLC10A3):​c.747G>A​(p.Met249Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000149 in 1,210,084 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 4 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000089 (0 hom., 1 hem., cov: 24)
  • Exomes 𝑓: 0.000015 (0 hom. 3 hem.)
• Consequence: SLC10A3 NM_019848.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0510
• Publications: 0 publications found

Genes affected

SLC10A3 (HGNC:22979): (solute carrier family 10 member 3) This gene maps to a GC-rich region of the X chromosome and was identified by its proximity to a CpG island. It is thought to be a housekeeping gene. Alternative splicing results in multiple transcript variants encoding distinct isoforms.[provided by RefSeq, Dec 2008]

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.06256598).
• BS2: High Hemizygotes in GnomAdExome4 at 3 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_019848.5. 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
	SLC10A3	NM_019848.5	MANE Select	c.747G>A	p.Met249Ile	missense	Exon 2 of 2	NP_062822.1	P09131-1
	SLC10A3	NM_001142392.3		c.747G>A	p.Met249Ile	missense	Exon 3 of 3	NP_001135864.1	P09131-1
	SLC10A3	NM_001142391.3		c.660G>A	p.Met220Ile	missense	Exon 4 of 4	NP_001135863.1	P09131-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC10A3	ENST00000651600.1	MANE Select	c.747G>A	p.Met249Ile	missense	Exon 2 of 2	ENSP00000499188.1	P09131-1
	SLC10A3	ENST00000369649.8	TSL:1	c.660G>A	p.Met220Ile	missense	Exon 4 of 4	ENSP00000358663.4	P09131-2
	SLC10A3	ENST00000393586.1	TSL:5	c.912G>A	p.Met304Ile	missense	Exon 3 of 3	ENSP00000377211.1	A0A0A0MS43

Frequencies

GnomAD3 genomes AF: 0.00000890 AC: 1 AN: 112420 Hom.: 0 Cov.: 24

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000934

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000874 AC: 16 AN: 183146 AF XY: 0.0000442

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000547

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000221

GnomAD4 exome AF: 0.0000155 AC: 17 AN: 1097664 Hom.: 0 Cov.: 31 AF XY: 0.00000826 AC XY: 3 AN XY: 363310

African (AFR) AF: 0.00 AC: 0 AN: 26402

American (AMR) AF: 0.000483 AC: 17 AN: 35206

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19386

East Asian (EAS) AF: 0.00 AC: 0 AN: 30205

South Asian (SAS) AF: 0.00 AC: 0 AN: 54144

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40051

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4136

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 842046

Other (OTH) AF: 0.00 AC: 0 AN: 46088

GnomAD4 genome AF: 0.00000890 AC: 1 AN: 112420 Hom.: 0 Cov.: 24 AF XY: 0.0000289 AC XY: 1 AN XY: 34580

African (AFR) AF: 0.00 AC: 0 AN: 30898

American (AMR) AF: 0.0000934 AC: 1 AN: 10701

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2650

East Asian (EAS) AF: 0.00 AC: 0 AN: 3576

South Asian (SAS) AF: 0.00 AC: 0 AN: 2713

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6239

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 239

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 53193

Other (OTH) AF: 0.00 AC: 0 AN: 1531

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000453

ExAC AF: 0.0000988 AC: 12

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_addAF	Benign	-0.63	T
BayesDel_noAF	Benign	-0.79
CADD	Benign	22
DANN	Benign	0.97
DEOGEN2	Benign	0.041	T
FATHMM_MKL	Benign	0.58	D
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.069	D
MetaRNN	Benign	0.063	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	-0.90	N
PhyloP100		-0.051
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-0.89	N
REVEL	Benign	0.042
Sift	Benign	0.20	T
Sift4G	Benign	0.19	T
Polyphen		0.075	B
Vest4		0.30
MutPred		0.40		Gain of catalytic residue at L254 (P = 0.02)
MVP		0.068
MPC		0.61
ClinPred		0.060	T
GERP RS		3.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.33
gMVP		0.45
Mutation Taster		=100/0	polymorphism

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: rs782584318; hg19: chrX-153716533;