rs11078738

Variant names:

• chr17-8264282-T-A
• rs11078738
• NM_012393.3:c.1862T>A

Your query was ambiguous. Multiple possible variants found:

• chr17-8264282-T-A
• chr17-8264282-T-C

Variant summary

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

The NM_012393.3(PFAS):​c.1862T>A​(p.Leu621Gln) 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. 16/22 in silico tools predict 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)
• Consequence: PFAS NM_012393.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0540
• Publications: 29 publications found

Genes affected

PFAS (HGNC:8863): (phosphoribosylformylglycinamidine synthase) Purines are necessary for many cellular processes, including DNA replication, transcription, and energy metabolism. Ten enzymatic steps are required to synthesize inosine monophosphate (IMP) in the de novo pathway of purine biosynthesis. The enzyme encoded by this gene catalyzes the fourth step of IMP biosynthesis. [provided by RefSeq, Jul 2008]

ACMG classification

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 (MetaRNN=0.0487085).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012393.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PFAS	NM_012393.3	MANE Select	c.1862T>A	p.Leu621Gln	missense	Exon 16 of 28	NP_036525.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PFAS	ENST00000314666.11	TSL:1 MANE Select	c.1862T>A	p.Leu621Gln	missense	Exon 16 of 28	ENSP00000313490.6
	PFAS	ENST00000580356.5	TSL:2	n.*1392T>A		non_coding_transcript_exon	Exon 14 of 26	ENSP00000464671.1
	PFAS	ENST00000581288.1	TSL:4	n.300T>A		non_coding_transcript_exon	Exon 4 of 5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 52

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.068
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	1.5
DANN	Benign	0.15
DEOGEN2	Benign	0.022	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.058	N
LIST_S2	Benign	0.25	T
M_CAP	Benign	0.0051	T
MetaRNN	Benign	0.049	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-1.1	N
PhyloP100		0.054
PrimateAI	Benign	0.31	T
PROVEAN	Benign	0.99	N
REVEL	Benign	0.046
Sift	Benign	0.57	T
Sift4G	Benign	0.58	T
Polyphen		0.0	B
Vest4		0.18
MutPred		0.32		Loss of glycosylation at P620 (P = 0.0695)
MVP		0.48
MPC		0.24
ClinPred		0.034	T
GERP RS		1.5
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.0
Varity_R		0.029
gMVP		0.53

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: rs11078738; hg19: chr17-8167600;