5-132294955-C-T

Position:

chr5-132294955-C-T

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_003059.3(SLC22A4):c.339C>T(p.Cys113=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00321 in 1,604,958 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0021 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0033 ( 11 hom. )

Consequence

SLC22A4
NM_003059.3 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.377

Variant links:

Genes affected

SLC22A4 (HGNC:10968): (solute carrier family 22 member 4) Polyspecific organic cation transporters in the liver, kidney, intestine, and other organs are critical for elimination of many endogenous small organic cations as well as a wide array of drugs and environmental toxins. The encoded protein is an organic cation transporter and plasma integral membrane protein containing eleven putative transmembrane domains as well as a nucleotide-binding site motif. Transport by this protein is at least partially ATP-dependent. [provided by RefSeq, Jul 2008]

SLC22A4 links:

P4HA2 (HGNC:8547): (prolyl 4-hydroxylase subunit alpha 2) This gene encodes a component of prolyl 4-hydroxylase, a key enzyme in collagen synthesis composed of two identical alpha subunits and two beta subunits. The encoded protein is one of several different types of alpha subunits and provides the major part of the catalytic site of the active enzyme. In collagen and related proteins, prolyl 4-hydroxylase catalyzes the formation of 4-hydroxyproline that is essential to the proper three-dimensional folding of newly synthesized procollagen chains. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Jul 2008]

P4HA2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.48).

BP6

Variant 5-132294955-C-T is Benign according to our data. Variant chr5-132294955-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1669687.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-132294955-C-T is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=0.377 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 11 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
SLC22A4	NM_003059.3 linkuse as main transcript	c.339C>T	p.Cys113=	synonymous_variant	1/10	ENST00000200652.4
SLC22A4	XM_047417594.1 linkuse as main transcript	c.339C>T	p.Cys113=	synonymous_variant	1/8
SLC22A4	XM_011543589.3 linkuse as main transcript	c.339C>T	p.Cys113=	synonymous_variant	1/8
SLC22A4	XM_006714675.5 linkuse as main transcript	c.-86C>T		5_prime_UTR_variant	1/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
SLC22A4	ENST00000200652.4 linkuse as main transcript	c.339C>T	p.Cys113=	synonymous_variant	1/10	1	NM_003059.3	P1
P4HA2	ENST00000471826.1 linkuse as main transcript	n.138+223G>A		intron_variant, non_coding_transcript_variant		1
P4HA2	ENST00000431054.5 linkuse as main transcript	c.78+223G>A		intron_variant		4

Frequencies

GnomAD3 genomes

AF:

0.00212

AC:

322

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000531

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000589

Gnomad ASJ

AF:

0.000865

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.00574

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00323

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.00200

AC:

457

AN:

228704

Hom.:

AF XY:

0.00192

AC XY:

240

AN XY:

125110

show subpopulations

Gnomad AFR exome

AF:

0.000372

Gnomad AMR exome

AF:

0.000394

Gnomad ASJ exome

AF:

0.000522

Gnomad EAS exome

AF:

0.0000589

Gnomad SAS exome

AF:

0.000275

Gnomad FIN exome

AF:

0.00468

Gnomad NFE exome

AF:

0.00318

Gnomad OTH exome

AF:

0.00194

GnomAD4 exome

AF:

0.00332

AC:

4825

AN:

1452632

Hom.:

Cov.:

AF XY:

0.00313

AC XY:

2263

AN XY:

721892

show subpopulations

Gnomad4 AFR exome

AF:

0.000480

Gnomad4 AMR exome

AF:

0.000367

Gnomad4 ASJ exome

AF:

0.000424

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000329

Gnomad4 FIN exome

AF:

0.00442

Gnomad4 NFE exome

AF:

0.00397

Gnomad4 OTH exome

AF:

0.00208

GnomAD4 genome

AF:

0.00211

AC:

321

AN:

152326

Hom.:

Cov.:

AF XY:

0.00211

AC XY:

157

AN XY:

74492

show subpopulations

Gnomad4 AFR

AF:

0.000529

Gnomad4 AMR

AF:

0.000588

Gnomad4 ASJ

AF:

0.000865

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000622

Gnomad4 FIN

AF:

0.00574

Gnomad4 NFE

AF:

0.00322

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00236

Hom.:

Bravo

AF:

0.00166

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Oct 01, 2022	SLC22A4: BP4, BP7 -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 19, 2023	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Benign

0.95

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over