4-48483589-C-T

Variant names:

• chr4-48483589-C-T
• NM_152679.4:c.28C>T

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.28C>T​(p.Leu10Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000739 in 1,353,082 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 (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.4e-7 (0 hom.)
• Consequence: SLC10A4 NM_152679.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.126
• 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=0.052586764).

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.28C>T	p.Leu10Phe	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.28C>T	p.Leu10Phe	missense	Exon 1 of 3	ENSP00000273861.4	Q96EP9

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.39e-7 AC: 1 AN: 1353082 Hom.: 0 Cov.: 31 AF XY: 0.00000150 AC XY: 1 AN XY: 668646

African (AFR) AF: 0.00 AC: 0 AN: 27392

American (AMR) AF: 0.00 AC: 0 AN: 32308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23664

East Asian (EAS) AF: 0.00 AC: 0 AN: 29534

South Asian (SAS) AF: 0.00 AC: 0 AN: 76280

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39398

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5580

European-Non Finnish (NFE) AF: 9.41e-7 AC: 1 AN: 1062874

Other (OTH) AF: 0.00 AC: 0 AN: 56052

GnomAD4 genome Cov.: 32

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	0.061
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.79
CADD	Benign	14
DANN	Benign	0.96
DEOGEN2	Benign	0.012	T
Eigen	Benign	-0.90
Eigen_PC	Benign	-0.87
FATHMM_MKL	Benign	0.081	N
LIST_S2	Benign	0.43	T
M_CAP	Benign	0.029	D
MetaRNN	Benign	0.053	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.55	N
PhyloP100		0.13
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	-0.24	N
REVEL	Benign	0.063
Sift	Benign	0.12	T
Sift4G	Pathogenic	0.0	D
Polyphen		0.0	B
Vest4		0.074
MutPred		0.19		Loss of loop (P = 0.1242)
MVP		0.014
MPC		0.69
ClinPred		0.15	T
GERP RS		1.1
PromoterAI		0.021	Neutral
Varity_R		0.057
gMVP		0.11
Mutation Taster		=95/5	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

hg19: chr4-48485606;