4-48483584-C-A

Variant names:

• chr4-48483584-C-A
• rs762978234
• NM_152679.4:c.23C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_152679.4(SLC10A4):​c.23C>A​(p.Thr8Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000192 in 1,506,946 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 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. T8S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000021 (0 hom.)
• Consequence: SLC10A4 NM_152679.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.763
• Publications: 0 publications found

Genes affected

SLC10A4 (HGNC:22980): (solute carrier family 10 member 4) Predicted to enable bile acid:sodium symporter activity. Predicted to be involved in bile acid and bile salt transport and regulation of neurotransmitter loading into synaptic vesicle. Predicted to act upstream of or within adult behavior and response to xenobiotic stimulus. Predicted to be located in plasma membrane. Predicted to be integral component of membrane. Predicted to be active in cholinergic synapse; dopaminergic synapse; and serotonergic synapse. Predicted to be integral component of synaptic vesicle membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.055689663).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152679.4. 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
	SLC10A4	NM_152679.4	MANE Select	c.23C>A	p.Thr8Asn	missense	Exon 1 of 3	NP_689892.1	Q96EP9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC10A4	ENST00000273861.5	TSL:1 MANE Select	c.23C>A	p.Thr8Asn	missense	Exon 1 of 3	ENSP00000273861.4	Q96EP9

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 151884 Hom.: 0 Cov.: 32

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: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000180 AC: 2 AN: 111418 AF XY: 0.0000320

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000476

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000234

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000207 AC: 28 AN: 1355062 Hom.: 0 Cov.: 31 AF XY: 0.0000164 AC XY: 11 AN XY: 669818

African (AFR) AF: 0.0000364 AC: 1 AN: 27456

American (AMR) AF: 0.0000613 AC: 2 AN: 32614

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23686

East Asian (EAS) AF: 0.00 AC: 0 AN: 29698

South Asian (SAS) AF: 0.00 AC: 0 AN: 76392

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39638

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5584

European-Non Finnish (NFE) AF: 0.0000235 AC: 25 AN: 1063872

Other (OTH) AF: 0.00 AC: 0 AN: 56122

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 151884 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74184

African (AFR) AF: 0.00 AC: 0 AN: 41406

American (AMR) AF: 0.00 AC: 0 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4838

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10498

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67922

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.0000610 Hom.: 0

Bravo AF: 0.0000189

ExAC AF: 0.00000896 AC: 1

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	0.075
BayesDel_addAF	Benign	-0.53	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Benign	0.011	T
Eigen	Benign	-0.61
Eigen_PC	Benign	-0.58
FATHMM_MKL	Benign	0.29	N
LIST_S2	Benign	0.48	T
M_CAP	Uncertain	0.087	D
MetaRNN	Benign	0.056	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.97	L
PhyloP100		0.76
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	-0.38	N
REVEL	Benign	0.025
Sift	Uncertain	0.0060	D
Sift4G	Uncertain	0.019	D
Polyphen		0.099	B
Vest4		0.20
MutPred		0.21		Gain of disorder (P = 0.095)
MVP		0.014
MPC		1.7
ClinPred		0.060	T
GERP RS		3.3
PromoterAI		0.0081	Neutral
Varity_R		0.12
gMVP		0.24
Mutation Taster		=97/3	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: rs762978234; hg19: chr4-48485601;