Genetic Variant ENST00000471826.1:n.138+809G>T (chr5-132294369-C-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000471826.1(P4HA2):n.138+809G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

P4HA2
ENST00000471826.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.27

Publications

10 publications found

Variant links:

Genes affected

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:

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 Gene-Disease associations (from GenCC):

hearing loss, autosomal recessive
Inheritance: AR Classification: LIMITED Submitted by: ClinGen

SLC22A4 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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 (BayesDel_noAF=-0.74).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000471826.1. 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
	SLC22A4	NM_003059.3	MANE Select	c.-248C>A		upstream_gene	N/A	NP_003050.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
P4HA2	ENST00000471826.1	TSL:1	n.138+809G>T	intron	N/A
SLC22A4	ENST00000897522.1		c.-248C>A	5_prime_UTR	Exon 1 of 6	ENSP00000567581.1
P4HA2	ENST00000431054.5	TSL:4	c.78+809G>T	intron	N/A	ENSP00000391257.1	E7EPI9

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

402226

Hom.:

AF XY:

0.00

AC XY:

AN XY:

211052

African (AFR)

AF:

0.00

AC:

AN:

11182

American (AMR)

AF:

0.00

AC:

AN:

15028

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

12454

East Asian (EAS)

AF:

0.00

AC:

AN:

27150

South Asian (SAS)

AF:

0.00

AC:

AN:

40660

European-Finnish (FIN)

AF:

0.00

AC:

AN:

25380

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1782

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

245208

Other (OTH)

AF:

0.00

AC:

AN:

23382

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

1521

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

0.43

(source)

DANN

Benign

0.31

PhyloP100

-3.3

PromoterAI

-0.060

Neutral

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over