chrX-154488397-C-T

Variant names:

• chrX-154488397-C-T
• rs138863812
• NM_019848.5:c.544G>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_019848.5(SLC10A3):​c.544G>A​(p.Ala182Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00064 in 1,209,719 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 256 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 Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00033 (0 hom., 9 hem., cov: 24)
  • Exomes 𝑓: 0.00067 (0 hom. 247 hem.)
• Consequence: SLC10A3 NM_019848.5 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.67
• Publications: 1 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.015341133).
• BP6: Variant X-154488397-C-T is Benign according to our data. Variant chrX-154488397-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2352689.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Hemizygotes in GnomAd4 at 9 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.544G>A	p.Ala182Thr	missense	Exon 2 of 2	NP_062822.1	P09131-1
	SLC10A3	NM_001142392.3		c.544G>A	p.Ala182Thr	missense	Exon 3 of 3	NP_001135864.1	P09131-1
	SLC10A3	NM_001142391.3		c.457G>A	p.Ala153Thr	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.544G>A	p.Ala182Thr	missense	Exon 2 of 2	ENSP00000499188.1	P09131-1
	SLC10A3	ENST00000369649.8	TSL:1	c.457G>A	p.Ala153Thr	missense	Exon 4 of 4	ENSP00000358663.4	P09131-2
	SLC10A3	ENST00000393586.1	TSL:5	c.709G>A	p.Ala237Thr	missense	Exon 3 of 3	ENSP00000377211.1	A0A0A0MS43

Frequencies

GnomAD3 genomes AF: 0.000330 AC: 37 AN: 112078 Hom.: 0 Cov.: 24

Gnomad AFR AF: 0.0000972

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000470

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000835

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000490

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000464 AC: 85 AN: 183143 AF XY: 0.000517

Gnomad AFR exome AF: 0.000228

Gnomad AMR exome AF: 0.000474

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000649

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000686

Gnomad OTH exome AF: 0.000664

GnomAD4 exome AF: 0.000671 AC: 737 AN: 1097587 Hom.: 0 Cov.: 31 AF XY: 0.000680 AC XY: 247 AN XY: 363149

African (AFR) AF: 0.000189 AC: 5 AN: 26394

American (AMR) AF: 0.000426 AC: 15 AN: 35198

Ashkenazi Jewish (ASJ) AF: 0.0000516 AC: 1 AN: 19379

East Asian (EAS) AF: 0.000265 AC: 8 AN: 30204

South Asian (SAS) AF: 0.0000924 AC: 5 AN: 54137

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40161

Middle Eastern (MID) AF: 0.000242 AC: 1 AN: 4135

European-Non Finnish (NFE) AF: 0.000798 AC: 672 AN: 841894

Other (OTH) AF: 0.000651 AC: 30 AN: 46085

GnomAD4 genome AF: 0.000330 AC: 37 AN: 112132 Hom.: 0 Cov.: 24 AF XY: 0.000262 AC XY: 9 AN XY: 34300

African (AFR) AF: 0.0000969 AC: 3 AN: 30944

American (AMR) AF: 0.000469 AC: 5 AN: 10661

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2640

East Asian (EAS) AF: 0.000838 AC: 3 AN: 3580

South Asian (SAS) AF: 0.00 AC: 0 AN: 2677

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6129

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 217

European-Non Finnish (NFE) AF: 0.000490 AC: 26 AN: 53084

Other (OTH) AF: 0.00 AC: 0 AN: 1521

Alfa AF: 0.000513 Hom.: 14

Bravo AF: 0.000314

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.000346 AC: 1

ESP6500AA AF: 0.000522 AC: 2

ESP6500EA AF: 0.000446 AC: 3

ExAC AF: 0.000469 AC: 57

EpiCase AF: 0.000818

EpiControl AF: 0.000593

ClinVar

ClinVar submissions

Significance: Likely benign

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	0.061
BayesDel_addAF	Benign	-0.92	T
BayesDel_noAF	Benign	-1.2
CADD	Benign	0.0010
DANN	Benign	0.79
DEOGEN2	Benign	0.049	T
FATHMM_MKL	Benign	0.0083	N
LIST_S2	Benign	0.54	T
M_CAP	Benign	0.0016	T
MetaRNN	Benign	0.015	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.22	N
PhyloP100		-3.7
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-0.050	N
REVEL	Benign	0.039
Sift	Benign	0.73	T
Sift4G	Benign	0.52	T
Polyphen		0.0010	B
Vest4		0.014
MVP		0.13
MPC		0.46
ClinPred		0.0020	T
GERP RS		-11
Varity_R		0.032
gMVP		0.24
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: rs138863812; hg19: chrX-153716736;