4-48483845-C-A

Variant names:

• chr4-48483845-C-A
• rs138059488
• NM_152679.4:c.284C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_152679.4(SLC10A4):​c.284C>A​(p.Pro95Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000351 in 1,538,736 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000033 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000035 (0 hom.)
• Consequence: SLC10A4 NM_152679.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.93
• 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.

• BP4: Computational evidence support a benign effect (MetaRNN=0.07953569).

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.284C>A	p.Pro95Gln	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.284C>A	p.Pro95Gln	missense	Exon 1 of 3	ENSP00000273861.4	Q96EP9

Frequencies

GnomAD3 genomes AF: 0.0000328 AC: 5 AN: 152220 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000436 AC: 6 AN: 137754 AF XY: 0.0000535

Gnomad AFR exome AF: 0.000160

Gnomad AMR exome AF: 0.0000410

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000287

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000353 AC: 49 AN: 1386398 Hom.: 0 Cov.: 31 AF XY: 0.0000322 AC XY: 22 AN XY: 683746

African (AFR) AF: 0.0000644 AC: 2 AN: 31076

American (AMR) AF: 0.0000281 AC: 1 AN: 35576

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25042

East Asian (EAS) AF: 0.00113 AC: 40 AN: 35550

South Asian (SAS) AF: 0.0000635 AC: 5 AN: 78688

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 41950

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4084

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1076868

Other (OTH) AF: 0.0000174 AC: 1 AN: 57564

GnomAD4 genome AF: 0.0000328 AC: 5 AN: 152338 Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3 AN XY: 74502

African (AFR) AF: 0.0000240 AC: 1 AN: 41598

American (AMR) AF: 0.0000653 AC: 1 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000194 AC: 1 AN: 5164

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68022

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000227

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	0.13
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.016	T
Eigen	Benign	-0.33
Eigen_PC	Benign	-0.29
FATHMM_MKL	Benign	0.30	N
LIST_S2	Benign	0.52	T
M_CAP	Benign	0.062	D
MetaRNN	Benign	0.080	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.90	L
PhyloP100		1.9
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	-1.0	N
REVEL	Benign	0.054
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.021	D
Polyphen		0.47	P
Vest4		0.35
MVP		0.030
MPC		1.3
ClinPred		0.093	T
GERP RS		3.7
Varity_R		0.084
gMVP		0.38
Mutation Taster		=88/12	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: rs138059488; hg19: chr4-48485862;