19-42868978-C-T

Position:

• chr19-42868978-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001184825.2(PSG1):​c.766G>A​(p.Asp256Asn) 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. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PSG1 NM_001184825.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0780

Genes affected

PSG1 (HGNC:9514): (pregnancy specific beta-1-glycoprotein 1) The human placenta is a multihormonal endocrine organ that produces hormones, enzymes, and other molecules that support fetal survival and development. Pregnancy-specific beta-1-glycoprotein (PSBG, PSG) is a major product of the syncytiotrophoblast, reaching concentrations of 100 to 290 mg/l at term in the serum of pregnant women (Horne et al., 1976 [PubMed 971765]). PSG is a member of the immunoglobulin (Ig) superfamily (Watanabe and Chou, 1988 [PubMed 3257488]; Streydio et al., 1988 [PubMed 3260773]).[supplied by OMIM, Oct 2009]

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=0.07890919).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PSG1	NM_001184825.2	c.766G>A	p.Asp256Asn	missense_variant	4/6	ENST00000436291.7	NP_001171754.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PSG1	ENST00000436291.7	c.766G>A	p.Asp256Asn	missense_variant	4/6	1	NM_001184825.2	ENSP00000413041.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 18, 2023

The c.766G>A (p.D256N) alteration is located in exon 4 (coding exon 4) of the PSG1 gene. This alteration results from a G to A substitution at nucleotide position 766, causing the aspartic acid (D) at amino acid position 256 to be replaced by an asparagine (N). 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	0.14
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	0.72
DANN	Benign	0.095
DEOGEN2	Benign	0.0029	T;T;.;T;.;.
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.0047	N
LIST_S2	Benign	0.79	T;T;T;T;T;T
M_CAP	Benign	0.00034	T
MetaRNN	Benign	0.079	T;T;T;T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.4	L;.;L;.;L;L
PROVEAN	Benign	-1.4	N;.;.;D;N;N
REVEL	Benign	0.085
Sift	Benign	0.84	T;.;.;D;T;T
Sift4G	Benign	0.10	T;T;T;T;T;T
Polyphen		0.66	P;.;D;P;B;B
Vest4		0.20
MutPred		0.34		Gain of loop (P = 0.1069);.;Gain of loop (P = 0.1069);.;Gain of loop (P = 0.1069);Gain of loop (P = 0.1069);
MVP		0.18
MPC		0.032
ClinPred		0.082	T
GERP RS		0.28
Varity_R		0.048
gMVP		0.092

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: chr19-43373130; COSMIC: COSV99738749; COSMIC: COSV99738749;