1-24360902-T-C

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 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. 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

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.23742014).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STPG1	NM_001199013.2	c.877A>G	p.Asn293Asp	missense_variant	Exon 8 of 9	ENST00000337248.9	NP_001185942.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STPG1	ENST00000337248.9	c.877A>G	p.Asn293Asp	missense_variant	Exon 8 of 9	5	NM_001199013.2	ENSP00000337461.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 20, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.877A>G (p.N293D) alteration is located in exon 8 (coding exon 7) of the STPG1 gene. This alteration results from a A to G substitution at nucleotide position 877, causing the asparagine (N) at amino acid position 293 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

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;T;.
Eigen	Benign	0.10
Eigen_PC	Benign	0.17
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.71	.;T;T
M_CAP	Benign	0.0056	T
MetaRNN	Benign	0.24	T;T;T
MetaSVM	Benign	-0.63	T
MutationAssessor	Uncertain	2.6	M;M;.
PrimateAI	Benign	0.43	T
PROVEAN	Uncertain	-2.8	D;D;D
REVEL	Benign	0.11
Sift	Benign	0.12	T;T;T
Sift4G	Benign	0.49	T;T;T
Polyphen		0.46	P;P;B
Vest4		0.32
MutPred		0.22		Loss of MoRF binding (P = 0.0684);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

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-24687392;