Variant 5-43494582-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_198566.4(C5orf34):c.1172C>T(p.Ser391Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000247 in 1,598,076 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00025 ( 0 hom. )

Consequence

C5orf34
NM_198566.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.01

Variant links:

Genes affected

C5orf34 (HGNC:24738): (chromosome 5 open reading frame 34)

C5orf34 links:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
C5orf34	NM_198566.4 linkuse as main transcript	c.1172C>T	p.Ser391Leu	missense_variant	7/13	ENST00000306862.7	NP_940968.1
C5orf34-AS1	XR_007058763.1 linkuse as main transcript	n.182+6440G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
C5orf34	ENST00000306862.7 linkuse as main transcript	c.1172C>T	p.Ser391Leu	missense_variant	7/13	1	NM_198566.4	ENSP00000303490	P1
	ENST00000505645.1 linkuse as main transcript	n.329+6440G>A		intron_variant, non_coding_transcript_variant		5
C5orf34	ENST00000506213.1 linkuse as main transcript	n.24C>T		non_coding_transcript_exon_variant	1/5	2
C5orf34	ENST00000503655.2 linkuse as main transcript	c.376C>T	p.Gln126Ter	stop_gained, NMD_transcript_variant	3/4	5		ENSP00000426724

Frequencies

GnomAD3 genomes

AF:

0.000256

AC:

AN:

152168

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000470

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.000269

AC:

AN:

248808

Hom.:

AF XY:

0.000283

AC XY:

AN XY:

134424

show subpopulations

Gnomad AFR exome

AF:

0.0000618

Gnomad AMR exome

AF:

0.0000294

Gnomad ASJ exome

AF:

0.0000999

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000231

Gnomad NFE exome

AF:

0.000487

Gnomad OTH exome

AF:

0.000660

GnomAD4 exome

AF:

0.000246

AC:

356

AN:

1445908

Hom.:

Cov.:

AF XY:

0.000251

AC XY:

180

AN XY:

718340

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000226

Gnomad4 ASJ exome

AF:

0.0000775

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000360

Gnomad4 NFE exome

AF:

0.000298

Gnomad4 OTH exome

AF:

0.000101

GnomAD4 genome

AF:

0.000256

AC:

AN:

152168

Hom.:

Cov.:

AF XY:

0.000269

AC XY:

AN XY:

74348

show subpopulations

Gnomad4 AFR

AF:

0.0000965

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.000470

Gnomad4 OTH

AF:

0.000479

Alfa

AF:

0.000360

Hom.:

Bravo

AF:

0.000219

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000288

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 18, 2023

The c.1172C>T (p.S391L) alteration is located in exon 7 (coding exon 6) of the C5orf34 gene. This alteration results from a C to T substitution at nucleotide position 1172, causing the serine (S) at amino acid position 391 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.30

CADD

Uncertain

DANN

Uncertain

0.99

Eigen

Uncertain

0.57

Eigen_PC

Uncertain

0.56

FATHMM_MKL

Uncertain

0.81

M_CAP

Benign

0.022

MetaRNN

Uncertain

0.46

MetaSVM

Benign

-0.57

MutationTaster

Benign

0.95

PROVEAN

Uncertain

-3.0

REVEL

Benign

0.096

Sift

Benign

0.090

Sift4G

Uncertain

0.019

Vest4

0.76

MVP

0.46

MPC

0.064

ClinPred

0.39

GERP RS

5.0

gMVP

0.48

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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