rs1663288505

Variant names:

• chr1-213996927-A-C
• rs1663288505
• NM_001270616.2:c.392A>C

Your query was ambiguous. Multiple possible variants found:

• chr1-213996927-A-C
• chr1-213996927-A-G
• chr1-213996927-A-T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001270616.2(PROX1):​c.392A>C​(p.Asn131Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N131S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PROX1 NM_001270616.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.59
• Publications: 0 publications found

Genes affected

PROX1 (HGNC:9459): (prospero homeobox 1) The protein encoded by this gene is a member of the homeobox transcription factor family. Members of this family contain a homeobox domain that consists of a 60-amino acid helix-turn-helix structure that binds DNA and RNA. The protein encoded by this gene is conserved across vertebrates and may play an essential role during development. Altered levels of this protein have been reported in cancers of different organs, such as colon, brain, blood, breast, pancreas, liver and esophagus. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2012]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.42160434).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PROX1	NM_001270616.2	c.392A>C	p.Asn131Thr	missense_variant	Exon 2 of 5	ENST00000366958.9	NP_001257545.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PROX1	ENST00000366958.9	c.392A>C	p.Asn131Thr	missense_variant	Exon 2 of 5	1	NM_001270616.2	ENSP00000355925.4
PROX1	ENST00000435016.2	c.392A>C	p.Asn131Thr	missense_variant	Exon 2 of 5	1		ENSP00000400694.1
PROX1	ENST00000471129.1	c.392A>C	p.Asn131Thr	missense_variant	Exon 2 of 2	3		ENSP00000419517.1
PROX1	ENST00000607425.1	c.392A>C	p.Asn131Thr	missense_variant	Exon 2 of 2	3		ENSP00000475357.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.19	.;T;T;T;T;.
Eigen	Uncertain	0.67
Eigen_PC	Pathogenic	0.67
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.93	D;.;.;D;.;D
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.42	T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	.;L;L;L;L;.
PhyloP100		5.6
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	-2.1	N;N;N;N;N;.
REVEL	Benign	0.22
Sift	Benign	0.10	T;T;T;T;T;.
Sift4G	Pathogenic	0.0	D;T;T;T;T;D
Polyphen		1.0	.;D;D;D;D;.
Vest4		0.42, 0.43, 0.42, 0.43
MutPred		0.54		Gain of glycosylation at N131 (P = 0.0287);Gain of glycosylation at N131 (P = 0.0287);Gain of glycosylation at N131 (P = 0.0287);Gain of glycosylation at N131 (P = 0.0287);Gain of glycosylation at N131 (P = 0.0287);Gain of glycosylation at N131 (P = 0.0287);
MVP		0.57
MPC		1.7
ClinPred		0.88	D
GERP RS		5.6
Varity_R		0.29
gMVP		0.31
Mutation Taster		=32/68	disease causing

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: rs1663288505; hg19: chr1-214170270;