chr6-28534139-C-A

Variant names:

• chr6-28534139-C-A
• rs531172601
• NM_001509.3:c.638C>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_001509.3(GPX5):​c.638C>A​(p.Ala213Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000345 in 1,448,722 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000035 (0 hom.)
• Consequence: GPX5 NM_001509.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.192
• Publications: 1 publications found

Genes affected

GPX5 (HGNC:4557): (glutathione peroxidase 5) This gene belongs to the glutathione peroxidase family. It is specifically expressed in the epididymis in the mammalian male reproductive tract, and is androgen-regulated. Unlike several other characterized glutathione peroxidases, this enzyme is not a selenoprotein, lacking the selenocysteine residue. Thus, it is selenium-independent, and has been proposed to play a role in protecting the membranes of spermatozoa from the damaging effects of lipid peroxidation and/or preventing premature acrosome reaction. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Oct 2016]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.038354754).
• BP6: Variant 6-28534139-C-A is Benign according to our data. Variant chr6-28534139-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3102119.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001509.3. 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
	GPX5	NM_001509.3	MANE Select	c.638C>A	p.Ala213Glu	missense	Exon 5 of 5	NP_001500.1	O75715-1
	GPX5	NM_003996.3		c.*217C>A		3_prime_UTR	Exon 4 of 4	NP_003987.2	O75715-2
	GPX5	NR_144470.2		n.716C>A		non_coding_transcript_exon	Exon 4 of 4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPX5	ENST00000412168.7	TSL:1 MANE Select	c.638C>A	p.Ala213Glu	missense	Exon 5 of 5	ENSP00000392398.2	O75715-1
	GPX5	ENST00000442674.6	TSL:5	n.1013C>A		non_coding_transcript_exon	Exon 6 of 6
	GPX5	ENST00000469384.1	TSL:1	c.*217C>A		downstream_gene	N/A	ENSP00000419935.1	O75715-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000836 AC: 2 AN: 239236 AF XY: 0.0000154

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000916

Gnomad OTH exome AF: 0.000174

GnomAD4 exome AF: 0.00000345 AC: 5 AN: 1448722 Hom.: 0 Cov.: 31 AF XY: 0.00000694 AC XY: 5 AN XY: 720274

African (AFR) AF: 0.00 AC: 0 AN: 32934

American (AMR) AF: 0.00 AC: 0 AN: 42582

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25312

East Asian (EAS) AF: 0.00 AC: 0 AN: 39124

South Asian (SAS) AF: 0.00 AC: 0 AN: 83914

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53104

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5704

European-Non Finnish (NFE) AF: 0.00000271 AC: 3 AN: 1106332

Other (OTH) AF: 0.0000335 AC: 2 AN: 59716

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000854 Hom.: 0

ExAC AF: 0.00000824 AC: 1

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	0.32
DANN	Benign	0.26
DEOGEN2	Benign	0.049	T
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.0079	N
M_CAP	Benign	0.0028	T
MetaRNN	Benign	0.038	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.58	N
PhyloP100		-0.19
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.27	N
REVEL	Benign	0.026
Sift	Benign	0.91	T
Sift4G	Benign	0.47	T
Polyphen		0.0020	B
Vest4		0.10
MutPred		0.37		Loss of MoRF binding (P = 0.0363)
MVP		0.22
MPC		0.17
ClinPred		0.022	T
GERP RS		-8.8
Varity_R		0.081
gMVP		0.48
Mutation Taster		=88/12	polymorphism

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

Other links and lift over

dbSNP: rs531172601; hg19: chr6-28501916;