19-42925967-A-C

Position:

• chr19-42925967-A-C

Variant summary

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

The NM_002783.3(PSG7):​c.1049T>G​(p.Leu350Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PSG7 NM_002783.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.90

Genes affected

PSG7 (HGNC:9524): (pregnancy specific beta-1-glycoprotein 7) This gene is a member of the pregnancy-specific glycoprotein (PSG) gene family. The PSG genes are a subgroup of the carcinoembryonic antigen (CEA) family of immunoglobulin-like genes, and are found in a gene cluster at 19q13.1-q13.2 telomeric to another cluster of CEA-related genes. The PSG genes are expressed by placental trophoblasts and released into the maternal circulation during pregnancy, and are thought to be essential for maintenance of normal pregnancy. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2014]

PSG7 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PSG7	NM_002783.3	c.1049T>G	p.Leu350Arg	missense_variant	5/6	ENST00000406070.7	NP_002774.2
PSG7	NM_001206650.2	c.683T>G	p.Leu228Arg	missense_variant	4/5		NP_001193579.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PSG7	ENST00000406070.7	c.1049T>G	p.Leu350Arg	missense_variant	5/6	1	NM_002783.3	ENSP00000421986.1
PSG7	ENST00000623675.3	c.683T>G	p.Leu228Arg	missense_variant	4/5	1		ENSP00000485117.1
PSG7	ENST00000446844.3	c.1049T>G	p.Leu350Arg	missense_variant	5/5	5		ENSP00000470856.1
PSG7	ENST00000599226.2	n.1611T>G		non_coding_transcript_exon_variant	1/2	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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

Mar 28, 2024

The c.1049T>G (p.L350R) alteration is located in exon 5 (coding exon 5) of the PSG7 gene. This alteration results from a T to G substitution at nucleotide position 1049, causing the leucine (L) at amino acid position 350 to be replaced by an arginine (R). 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	Uncertain	0.45
BayesDel_addAF	Pathogenic	0.34	D
BayesDel_noAF	Pathogenic	0.25
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.084	T;.;.
FATHMM_MKL	Benign	0.029	N
LIST_S2	Uncertain	0.95	D;D;D
MetaRNN	Uncertain	0.64	D;D;D
PrimateAI	Benign	0.44	T
Sift4G	Uncertain	0.0020	D;D;D
Polyphen		1.0	D;.;.
Vest4		0.73
MVP		0.14
GERP RS		1.3
Varity_R		0.15
gMVP		0.22

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: chr19-43430119;