19-42925946-T-C

Position:

• chr19-42925946-T-C

Variant summary

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

The NM_002783.3(PSG7):​c.1070A>G​(p.Asp357Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,638 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 8/12 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)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: PSG7 NM_002783.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.871

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12623134).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PSG7	NM_002783.3	c.1070A>G	p.Asp357Gly	missense_variant	5/6	ENST00000406070.7	NP_002774.2
PSG7	NM_001206650.2	c.704A>G	p.Asp235Gly	missense_variant	4/5		NP_001193579.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PSG7	ENST00000406070.7	c.1070A>G	p.Asp357Gly	missense_variant	5/6	1	NM_002783.3	ENSP00000421986.1
PSG7	ENST00000623675.3	c.704A>G	p.Asp235Gly	missense_variant	4/5	1		ENSP00000485117.1
PSG7	ENST00000446844.3	c.1070A>G	p.Asp357Gly	missense_variant	5/5	5		ENSP00000470856.1
PSG7	ENST00000599226.2	n.1632A>G		non_coding_transcript_exon_variant	1/2	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460638 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 726572

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

Bravo AF: 0.0000189

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

Jan 17, 2024

The c.1070A>G (p.D357G) alteration is located in exon 5 (coding exon 5) of the PSG7 gene. This alteration results from a A to G substitution at nucleotide position 1070, causing the aspartic acid (D) at amino acid position 357 to be replaced by a glycine (G). 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	0.15
BayesDel_addAF	Uncertain	0.064	T
BayesDel_noAF	Benign	-0.15
CADD	Benign	14
DANN	Benign	0.82
DEOGEN2	Benign	0.019	T;.;.
FATHMM_MKL	Benign	0.0041	N
LIST_S2	Benign	0.82	T;D;T
MetaRNN	Benign	0.13	T;T;T
PrimateAI	Benign	0.42	T
Sift4G	Uncertain	0.043	D;T;D
Polyphen		0.27	B;.;.
Vest4		0.25
MVP		0.040
GERP RS		-2.7
Varity_R		0.064
gMVP		0.096

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

LitVar

Other links and lift over

dbSNP: rs1423068289; hg19: chr19-43430098;