5-43506087-A-C

Position:

• chr5-43506087-A-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_198566.4(C5orf34):​c.593T>G​(p.Phe198Cys) variant causes a missense 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. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: C5orf34 NM_198566.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0910

Genes affected

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

(HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.044016063).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
C5orf34	NM_198566.4	c.593T>G	p.Phe198Cys	missense_variant	4/13	ENST00000306862.7	NP_940968.1
C5orf34-AS1	XR_007058763.1	n.183-121A>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
C5orf34	ENST00000306862.7	c.593T>G	p.Phe198Cys	missense_variant	4/13	1	NM_198566.4	ENSP00000303490	P1
	ENST00000505645.1	n.330-3117A>C		intron_variant, non_coding_transcript_variant		5
C5orf34	ENST00000509489.1	c.251T>G	p.Phe84Cys	missense_variant	2/3	3		ENSP00000424486
C5orf34	ENST00000514462.1	n.671T>G		non_coding_transcript_exon_variant	3/3	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 17, 2021

The c.593T>G (p.F198C) alteration is located in exon 4 (coding exon 3) of the C5orf34 gene. This alteration results from a T to G substitution at nucleotide position 593, causing the phenylalanine (F) at amino acid position 198 to be replaced by a cysteine (C). 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	0.074
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	7.7
DANN	Benign	0.89
Eigen	Benign	-0.56
Eigen_PC	Benign	-0.52
FATHMM_MKL	Benign	0.087	N
LIST_S2	Benign	0.41	.;T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.044	T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	N
PROVEAN	Benign	0.76	N;N
REVEL	Benign	0.063
Sift	Benign	0.19	T;T
Sift4G	Benign	0.19	T;.
Vest4		0.10
MutPred		0.22		Loss of stability (P = 0.0624);.;
MVP		0.16
MPC		0.034
ClinPred		0.13	T
GERP RS		2.8
gMVP		0.19

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-43506189;