chrX-154487628-C-T

Variant names:

• chrX-154487628-C-T
• rs1186667852
• NM_019848.5:c.1313G>A

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_019848.5(SLC10A3):​c.1313G>A​(p.Arg438His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000827 in 1,208,782 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 8 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R438L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000036 (0 hom., 4 hem., cov: 25)
  • Exomes 𝑓: 0.0000055 (0 hom. 4 hem.)
• Consequence: SLC10A3 NM_019848.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.12
• 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.1643455).
• BS2: High Hemizygotes in GnomAd4 at 4 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.1313G>A	p.Arg438His	missense	Exon 2 of 2	NP_062822.1	P09131-1
	SLC10A3	NM_001142392.3		c.1313G>A	p.Arg438His	missense	Exon 3 of 3	NP_001135864.1	P09131-1
	SLC10A3	NM_001142391.3		c.1226G>A	p.Arg409His	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.1313G>A	p.Arg438His	missense	Exon 2 of 2	ENSP00000499188.1	P09131-1
	SLC10A3	ENST00000369649.8	TSL:1	c.1226G>A	p.Arg409His	missense	Exon 4 of 4	ENSP00000358663.4	P09131-2
	SLC10A3	ENST00000393586.1	TSL:5	c.1478G>A	p.Arg493His	missense	Exon 3 of 3	ENSP00000377211.1	A0A0A0MS43

Frequencies

GnomAD3 genomes AF: 0.0000357 AC: 4 AN: 112131 Hom.: 0 Cov.: 25

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000943

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000373

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000376

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000554 AC: 1 AN: 180555 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000125

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000547 AC: 6 AN: 1096651 Hom.: 0 Cov.: 31 AF XY: 0.0000110 AC XY: 4 AN XY: 362537

African (AFR) AF: 0.00 AC: 0 AN: 26394

American (AMR) AF: 0.00 AC: 0 AN: 35128

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19323

East Asian (EAS) AF: 0.00 AC: 0 AN: 30201

South Asian (SAS) AF: 0.0000185 AC: 1 AN: 54031

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39731

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4129

European-Non Finnish (NFE) AF: 0.00000594 AC: 5 AN: 841669

Other (OTH) AF: 0.00 AC: 0 AN: 46045

GnomAD4 genome AF: 0.0000357 AC: 4 AN: 112131 Hom.: 0 Cov.: 25 AF XY: 0.000116 AC XY: 4 AN XY: 34339

African (AFR) AF: 0.00 AC: 0 AN: 30881

American (AMR) AF: 0.0000943 AC: 1 AN: 10607

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2635

East Asian (EAS) AF: 0.00 AC: 0 AN: 3567

South Asian (SAS) AF: 0.000373 AC: 1 AN: 2680

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6187

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 240

European-Non Finnish (NFE) AF: 0.0000376 AC: 2 AN: 53133

Other (OTH) AF: 0.00 AC: 0 AN: 1517

Alfa AF: 0.0000712 Hom.: 0

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	0.10
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	18
DANN	Uncertain	1.0
DEOGEN2	Benign	0.072	T
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.0093	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L
PhyloP100		1.1
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-0.92	N
REVEL	Benign	0.075
Sift	Benign	0.073	T
Sift4G	Benign	0.099	T
Polyphen		0.86	P
Vest4		0.14
MutPred		0.36		Gain of helix (P = 0.0696)
MVP		0.22
MPC		0.62
ClinPred		0.61	D
GERP RS		4.2
Varity_R		0.13
gMVP		0.43
Mutation Taster		=82/18	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: rs1186667852; hg19: chrX-153715967;