NM_019848.5:c.454G>A

Variant names:

• chrX-154488487-C-T
• rs782596898
• NM_019848.5:c.454G>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.454G>A​(p.Ala152Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000364 in 1,208,465 control chromosomes in the GnomAD database, including 1 homozygotes. There are 17 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 0.000054 (1 hom., 1 hem., cov: 24)
  • Exomes 𝑓: 0.000035 (0 hom. 16 hem.)
• Consequence: SLC10A3 NM_019848.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.793
• 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=0.042000264).
• BS2: High Hemizygotes in GnomAdExome4 at 16 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.454G>A	p.Ala152Thr	missense	Exon 2 of 2	NP_062822.1	P09131-1
	SLC10A3	NM_001142392.3		c.454G>A	p.Ala152Thr	missense	Exon 3 of 3	NP_001135864.1	P09131-1
	SLC10A3	NM_001142391.3		c.367G>A	p.Ala123Thr	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.454G>A	p.Ala152Thr	missense	Exon 2 of 2	ENSP00000499188.1	P09131-1
	SLC10A3	ENST00000369649.8	TSL:1	c.367G>A	p.Ala123Thr	missense	Exon 4 of 4	ENSP00000358663.4	P09131-2
	SLC10A3	ENST00000393586.1	TSL:5	c.619G>A	p.Ala207Thr	missense	Exon 3 of 3	ENSP00000377211.1	A0A0A0MS43

Frequencies

GnomAD3 genomes AF: 0.0000537 AC: 6 AN: 111677 Hom.: 1 Cov.: 24

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000283

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000374

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000377

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000439 AC: 8 AN: 182358 AF XY: 0.0000298

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000110

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000493

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000346 AC: 38 AN: 1096734 Hom.: 0 Cov.: 31 AF XY: 0.0000441 AC XY: 16 AN XY: 362484

African (AFR) AF: 0.0000379 AC: 1 AN: 26385

American (AMR) AF: 0.0000569 AC: 2 AN: 35177

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19363

East Asian (EAS) AF: 0.00 AC: 0 AN: 30179

South Asian (SAS) AF: 0.0000739 AC: 4 AN: 54097

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40016

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4127

European-Non Finnish (NFE) AF: 0.0000357 AC: 30 AN: 841363

Other (OTH) AF: 0.0000217 AC: 1 AN: 46027

GnomAD4 genome AF: 0.0000537 AC: 6 AN: 111731 Hom.: 1 Cov.: 24 AF XY: 0.0000295 AC XY: 1 AN XY: 33935

African (AFR) AF: 0.00 AC: 0 AN: 30760

American (AMR) AF: 0.000282 AC: 3 AN: 10625

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 3545

South Asian (SAS) AF: 0.000376 AC: 1 AN: 2663

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6094

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

European-Non Finnish (NFE) AF: 0.0000378 AC: 2 AN: 52977

Other (OTH) AF: 0.00 AC: 0 AN: 1515

Alfa AF: 0.000216 Hom.: 1

Bravo AF: 0.0000453

TwinsUK AF: 0.000539 AC: 2

ALSPAC AF: 0.00 AC: 0

ExAC AF: 0.0000247 AC: 3

EpiCase AF: 0.00

EpiControl AF: 0.000119

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	0.064
BayesDel_addAF	Benign	-0.74	T
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.013
DANN	Benign	0.76
DEOGEN2	Benign	0.038	T
FATHMM_MKL	Benign	0.034	N
LIST_S2	Benign	0.36	T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.042	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	1.1	L
PhyloP100		0.79
PrimateAI	Benign	0.32	T
PROVEAN	Benign	0.15	N
REVEL	Benign	0.021
Sift	Benign	0.54	T
Sift4G	Benign	0.51	T
Polyphen		0.079	B
Vest4		0.055
MVP		0.22
MPC		0.46
ClinPred		0.019	T
GERP RS		-0.087
Varity_R		0.042
gMVP		0.16
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: rs782596898; hg19: chrX-153716826;