Genetic Variant NM_180991.5:c.2084C>T (chr5-102236949-G-A) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_180991.5(SLCO4C1):c.2084C>T(p.Ser695Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,406 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

SLCO4C1
NM_180991.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.276

Publications

0 publications found

Variant links:

Genes affected

SLCO4C1 (HGNC:23612): (solute carrier organic anion transporter family member 4C1) SLCO4C1 belongs to the organic anion transporter (OATP) family. OATPs are involved in the membrane transport of bile acids, conjugated steroids, thyroid hormone, eicosanoids, peptides, and numerous drugs in many tissues (Mikkaichi et al., 2004 [PubMed 14993604]).[supplied by OMIM, Mar 2008]

SLCO4C1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.058848888).

BP6

Variant 5-102236949-G-A is Benign according to our data. Variant chr5-102236949-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3165868.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLCO4C1	NM_180991.5 link	c.2084C>T	p.Ser695Leu	missense_variant	Exon 13 of 13	ENST00000310954.7	NP_851322.3	Q6ZQN7
SLCO4C1	XM_011543370.3 link	c.1820C>T	p.Ser607Leu	missense_variant	Exon 12 of 12		XP_011541672.1
SLCO4C1	XM_011543372.2 link	c.1670C>T	p.Ser557Leu	missense_variant	Exon 15 of 15		XP_011541674.1
SLCO4C1	XM_047417146.1 link	c.1670C>T	p.Ser557Leu	missense_variant	Exon 15 of 15		XP_047273102.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLCO4C1	ENST00000310954.7 link	c.2084C>T	p.Ser695Leu	missense_variant	Exon 13 of 13	1	NM_180991.5	ENSP00000309741.6		Q6ZQN7

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1460406

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726524

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33452

American (AMR)

AF:

0.00

AC:

AN:

44622

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26112

East Asian (EAS)

AF:

0.00

AC:

AN:

39584

South Asian (SAS)

AF:

0.00

AC:

AN:

86040

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52890

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5760

European-Non Finnish (NFE)

AF:

9.00e-7

AC:

AN:

1111602

Other (OTH)

AF:

0.00

AC:

AN:

60344

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Jan 03, 2024

Ambry Genetics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.059

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.75

CADD

Benign

4.4

(source)

DANN

Benign

0.72

DEOGEN2

Benign

0.033

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.035

LIST_S2

Benign

0.66

M_CAP

Benign

0.0041

MetaRNN

Benign

0.059

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.42

PhyloP100

0.28

PrimateAI

Benign

0.26

PROVEAN

Benign

-1.3

REVEL

Benign

0.084

Sift

Benign

0.32

Sift4G

Benign

0.30

Polyphen

0.0

Vest4

0.044

MutPred

0.31

Loss of disorder (P = 0.0043);

MVP

0.14

MPC

0.039

ClinPred

0.20

GERP RS

0.51

Varity_R

0.040

gMVP

0.13

Mutation Taster

=94/6

polymorphism

(source)

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

Publications

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NM_180991.5:c.2084C>T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over