4-48483710-T-C

Variant names:

• chr4-48483710-T-C
• rs781272390
• NM_152679.4:c.149T>C

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.149T>C​(p.Leu50Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000156 in 1,278,942 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 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. L50F) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000016 (0 hom.)
• Consequence: SLC10A4 NM_152679.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.124
• 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=0.055909336).

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.149T>C	p.Leu50Pro	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.149T>C	p.Leu50Pro	missense	Exon 1 of 3	ENSP00000273861.4	Q96EP9

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00 AC: 0 AN: 42852 AF XY: 0.00

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: 0.00000156 AC: 2 AN: 1278942 Hom.: 0 Cov.: 27 AF XY: 0.00000318 AC XY: 2 AN XY: 629602

African (AFR) AF: 0.00 AC: 0 AN: 24640

American (AMR) AF: 0.00 AC: 0 AN: 16868

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20238

East Asian (EAS) AF: 0.00 AC: 0 AN: 28710

South Asian (SAS) AF: 0.0000305 AC: 2 AN: 65680

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32638

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4594

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1032700

Other (OTH) AF: 0.00 AC: 0 AN: 52874

GnomAD4 genome Cov.: 32

ExAC AF: 0.0000369 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	0.048
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	15
DANN	Benign	0.74
DEOGEN2	Benign	0.0024	T
Eigen	Benign	-0.92
Eigen_PC	Benign	-0.93
FATHMM_MKL	Benign	0.16	N
LIST_S2	Benign	0.40	T
M_CAP	Benign	0.030	D
MetaRNN	Benign	0.056	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.81	L
PhyloP100		0.12
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	-0.050	N
REVEL	Benign	0.076
Sift	Uncertain	0.0090	D
Sift4G	Uncertain	0.0080	D
Polyphen		0.0	B
Vest4		0.18
MutPred		0.11		Loss of glycosylation at P46 (P = 0.0235)
MVP		0.088
MPC		1.3
ClinPred		0.062	T
GERP RS		1.8
PromoterAI		0.063	Neutral
Varity_R		0.20
gMVP		0.56
Mutation Taster		=92/8	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: rs781272390; hg19: chr4-48485727;