PXT1 p.Gln104His

Variant names:

• chr6-36391863-C-A
• NM_152990.4:c.312G>T
• PXT1 p.Gln104His

Your query was ambiguous. Multiple possible variants found:

• chr6-36391863-C-A
• chr6-36391863-C-G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_152990.4(PXT1):​c.312G>T​(p.Gln104His) 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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PXT1 NM_152990.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.296
• Publications: 0 publications found

Genes affected

PXT1 (HGNC:18312): (peroxisomal testis enriched protein 1) Predicted to be involved in positive regulation of apoptotic process. Predicted to act upstream of or within spermatogenesis. Predicted to be active in nucleus and peroxisome. [provided by Alliance of Genome Resources, Apr 2022]

ETV7-AS1 (HGNC:40833): (ETV7 and PTX1 antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1324907).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152990.4. 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
	PXT1	NM_152990.4	MANE Select	c.312G>T	p.Gln104His	missense	Exon 5 of 5	NP_694535.2	Q8NFP0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PXT1	ENST00000454782.3	TSL:1 MANE Select	c.312G>T	p.Gln104His	missense	Exon 5 of 5	ENSP00000419944.1	Q8NFP0
	ETV7-AS1	ENST00000411643.1	TSL:3	n.188C>A		non_coding_transcript_exon	Exon 2 of 2
	ETV7-AS1	ENST00000841099.1		n.165C>A		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Benign	-0.093	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	19
DANN	Benign	0.97
DEOGEN2	Benign	0.064	T
Eigen	Benign	-0.31
Eigen_PC	Benign	-0.40
FATHMM_MKL	Benign	0.31	N
LIST_S2	Benign	0.48	T
M_CAP	Benign	0.0089	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.90	L
PhyloP100		0.30
PrimateAI	Benign	0.29	T
PROVEAN	Pathogenic	-4.7	D
REVEL	Benign	0.057
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Varity_R		0.47
gMVP		0.078
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		Details are displayed if max score is > 0.2

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr6-36359640;