NM_019848.5:c.952G>A

Variant names:

• chrX-154487989-C-T
• rs782319797
• NM_019848.5:c.952G>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.952G>A​(p.Val318Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000496 in 1,209,702 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 30 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000045 (0 hom., 2 hem., cov: 24)
  • Exomes 𝑓: 0.000050 (0 hom. 28 hem.)
• Consequence: SLC10A3 NM_019848.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.59
• 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=0.17109829).
• BS2: High Hemizygotes in GnomAd4 at 2 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.952G>A	p.Val318Met	missense	Exon 2 of 2	NP_062822.1	P09131-1
	SLC10A3	NM_001142392.3		c.952G>A	p.Val318Met	missense	Exon 3 of 3	NP_001135864.1	P09131-1
	SLC10A3	NM_001142391.3		c.865G>A	p.Val289Met	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.952G>A	p.Val318Met	missense	Exon 2 of 2	ENSP00000499188.1	P09131-1
	SLC10A3	ENST00000369649.8	TSL:1	c.865G>A	p.Val289Met	missense	Exon 4 of 4	ENSP00000358663.4	P09131-2
	SLC10A3	ENST00000393586.1	TSL:5	c.1117G>A	p.Val373Met	missense	Exon 3 of 3	ENSP00000377211.1	A0A0A0MS43

Frequencies

GnomAD3 genomes AF: 0.0000447 AC: 5 AN: 111915 Hom.: 0 Cov.: 24

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000754

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000565

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000382 AC: 7 AN: 183110 AF XY: 0.0000590

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000365

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000722

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000367

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000501 AC: 55 AN: 1097732 Hom.: 0 Cov.: 31 AF XY: 0.0000771 AC XY: 28 AN XY: 363360

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

American (AMR) AF: 0.0000284 AC: 1 AN: 35206

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19385

East Asian (EAS) AF: 0.0000331 AC: 1 AN: 30206

South Asian (SAS) AF: 0.000148 AC: 8 AN: 54147

European-Finnish (FIN) AF: 0.0000250 AC: 1 AN: 40071

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

European-Non Finnish (NFE) AF: 0.0000523 AC: 44 AN: 842088

Other (OTH) AF: 0.00 AC: 0 AN: 46091

GnomAD4 genome AF: 0.0000447 AC: 5 AN: 111970 Hom.: 0 Cov.: 24 AF XY: 0.0000586 AC XY: 2 AN XY: 34154

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 30926

American (AMR) AF: 0.00 AC: 0 AN: 10630

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2637

East Asian (EAS) AF: 0.00 AC: 0 AN: 3563

South Asian (SAS) AF: 0.000756 AC: 2 AN: 2645

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6081

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 216

European-Non Finnish (NFE) AF: 0.0000565 AC: 3 AN: 53054

Other (OTH) AF: 0.00 AC: 0 AN: 1533

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.0338994), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.000214 Hom.: 1

Bravo AF: 0.0000718

ExAC AF: 0.0000577 AC: 7

EpiCase AF: 0.0000545

EpiControl AF: 0.000237

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	0.27
BayesDel_addAF	Benign	-0.46	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.091	T
FATHMM_MKL	Benign	0.74	D
LIST_S2	Uncertain	0.91	D
M_CAP	Pathogenic	0.29	D
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		2.6
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.16
Sift	Uncertain	0.028	D
Sift4G	Benign	0.068	T
Polyphen		0.94	P
Vest4		0.23
MutPred		0.51		Gain of helix (P = 0.0425)
MVP		0.39
MPC		0.94
ClinPred		0.18	T
GERP RS		3.3
Varity_R		0.22
gMVP		0.83
Mutation Taster		=96/4	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: rs782319797; hg19: chrX-153716328; COSMIC: COSV99682173; COSMIC: COSV99682173;