NM_001199013.2:c.877A>G

Variant names:

• chr1-24360902-T-C
• NM_001199013.2:c.877A>G

Variant summary

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

The NM_001199013.2(STPG1):​c.877A>G​(p.Asn293Asp) 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. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N293S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: STPG1 NM_001199013.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.74
• Publications: 0 publications found

Genes affected

STPG1 (HGNC:28070): (sperm tail PG-rich repeat containing 1) Involved in positive regulation of apoptotic process and positive regulation of mitochondrial membrane permeability involved in apoptotic process. Predicted to be located in mitochondrion and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

GRHL3 (HGNC:25839): (grainyhead like transcription factor 3) This gene encodes a member of the grainyhead family of transcription factors. The encoded protein may function as a transcription factor during development, and has been shown to stimulate migration of endothelial cells. Multiple transcript variants encoding distinct isoforms have been identified for this gene.[provided by RefSeq, Aug 2010]

GRHL3 Gene-Disease associations (from GenCC):

• van der Woude syndrome 2

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
• van der Woude syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

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=0.23742014).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001199013.2. 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
	STPG1	NM_001199013.2	MANE Select	c.877A>G	p.Asn293Asp	missense	Exon 8 of 9	NP_001185942.1	Q5TH74-1
	STPG1	NM_001199012.2		c.877A>G	p.Asn293Asp	missense	Exon 8 of 9	NP_001185941.1	Q5TH74-1
	STPG1	NM_178122.5		c.736A>G	p.Asn246Asp	missense	Exon 7 of 8	NP_835223.1	Q5TH74-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STPG1	ENST00000337248.9	TSL:5 MANE Select	c.877A>G	p.Asn293Asp	missense	Exon 8 of 9	ENSP00000337461.4	Q5TH74-1
	STPG1	ENST00000468303.5	TSL:1	n.4350A>G		non_coding_transcript_exon	Exon 9 of 10
	STPG1	ENST00000374409.5	TSL:2	c.877A>G	p.Asn293Asp	missense	Exon 8 of 9	ENSP00000363530.1	Q5TH74-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

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	0.20
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.039	T
Eigen	Benign	0.10
Eigen_PC	Benign	0.17
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.0056	T
MetaRNN	Benign	0.24	T
MetaSVM	Benign	-0.63	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		3.7
PrimateAI	Benign	0.43	T
PROVEAN	Uncertain	-2.8	D
REVEL	Benign	0.11
Sift	Benign	0.12	T
Sift4G	Benign	0.49	T
Polyphen		0.46	P
Vest4		0.32
MutPred		0.22		Loss of MoRF binding (P = 0.0684)
MVP		0.25
MPC		0.47
ClinPred		0.91	D
GERP RS		4.7
Varity_R		0.20
gMVP		0.44
Mutation Taster		=92/8	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

hg19: chr1-24687392;