5-132294880-C-T

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7

The NM_003059.3(SLC22A4):c.264C>T(p.Thr88=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000562 in 1,601,264 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00035 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000026 ( 0 hom. )

Consequence

SLC22A4
NM_003059.3 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.228

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 Likely_benign. Variant got -5 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.65).

BP6

Variant 5-132294880-C-T is Benign according to our data. Variant chr5-132294880-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2044715.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr5-132294880-C-T is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=-0.228 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
SLC22A4	NM_003059.3 linkuse as main transcript	c.264C>T	p.Thr88=	synonymous_variant	1/10	ENST00000200652.4
SLC22A4	XM_047417594.1 linkuse as main transcript	c.264C>T	p.Thr88=	synonymous_variant	1/8
SLC22A4	XM_011543589.3 linkuse as main transcript	c.264C>T	p.Thr88=	synonymous_variant	1/8
SLC22A4	XM_006714675.5 linkuse as main transcript	c.-161C>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.264C>T	p.Thr88=	synonymous_variant	1/10	1	NM_003059.3	P1
P4HA2	ENST00000471826.1 linkuse as main transcript	n.138+298G>A		intron_variant, non_coding_transcript_variant		1
P4HA2	ENST00000431054.5 linkuse as main transcript	c.78+298G>A		intron_variant		4

Frequencies

GnomAD3 genomes

AF:

0.000348

AC:

AN:

152232

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00111

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000458

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000653

AC:

AN:

214480

Hom.:

AF XY:

0.0000590

AC XY:

AN XY:

118586

show subpopulations

Gnomad AFR exome

AF:

0.00109

Gnomad AMR exome

AF:

0.0000316

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS 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:

0.0000255

AC:

AN:

1449032

Hom.:

Cov.:

AF XY:

0.0000236

AC XY:

AN XY:

720212

show subpopulations

Gnomad4 AFR exome

AF:

0.000842

Gnomad4 AMR exome

AF:

0.0000937

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000835

GnomAD4 genome

AF:

0.000348

AC:

AN:

152232

Hom.:

Cov.:

AF XY:

0.000403

AC XY:

AN XY:

74372

show subpopulations

Gnomad4 AFR

AF:

0.00111

Gnomad4 AMR

AF:

0.000458

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000427

Hom.:

Bravo

AF:

0.000434

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Jan 25, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.65

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