Genetic Variant SLC10A4:p.Thr8Ser (chr4-48483584-C-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_152679.4(SLC10A4):c.23C>G(p.Thr8Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000517 in 1,355,062 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T8N) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000052 ( 0 hom. )

Consequence

SLC10A4
NM_152679.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.763

Publications

0 publications found

Variant links:

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]

SLC10A4 links:

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ACMG classification

Classification was made for transcript

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=0.0649268).

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>G	p.Thr8Ser	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>G	p.Thr8Ser	missense	Exon 1 of 3	ENSP00000273861.4	Q96EP9

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000269

AC:

AN:

111418

AF XY:

0.0000480

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000517

AC:

AN:

1355062

Hom.:

Cov.:

AF XY:

0.00000896

AC XY:

AN XY:

669818

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

27456

American (AMR)

AF:

0.00

AC:

AN:

32614

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23686

East Asian (EAS)

AF:

0.00

AC:

AN:

29698

South Asian (SAS)

AF:

0.0000916

AC:

AN:

76392

European-Finnish (FIN)

AF:

0.00

AC:

AN:

39638

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5584

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1063872

Other (OTH)

AF:

0.00

AC:

AN:

56122

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.411

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000179

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.065

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.73

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0083

Eigen

Benign

-0.67

Eigen_PC

Benign

-0.63

FATHMM_MKL

Benign

0.24

LIST_S2

Benign

0.31

M_CAP

Benign

0.081

MetaRNN

Benign

0.065

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.97

PhyloP100

0.76

PrimateAI

Uncertain

0.70

PROVEAN

Benign

-0.36

REVEL

Benign

0.038

Sift

Benign

0.10

Sift4G

Benign

0.25

Polyphen

0.0030

Vest4

0.098

MutPred

0.21

Gain of disorder (P = 0.0707)

MVP

0.014

MPC

1.5

ClinPred

0.16

GERP RS

3.3

PromoterAI

0.033

Neutral

(source)

Varity_R

0.085

gMVP

0.13

Mutation Taster

=96/4

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over