chr19-42926013-G-C

Variant names:

• chr19-42926013-G-C
• rs1205049115
• NM_002783.3:c.1003C>G

Variant summary

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

The NM_002783.3(PSG7):​c.1003C>G​(p.Pro335Ala) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P335S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PSG7 NM_002783.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.214
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PSG7	NM_002783.3	c.1003C>G	p.Pro335Ala	missense_variant	Exon 5 of 6	ENST00000406070.7	NP_002774.2
PSG7	NM_001206650.2	c.637C>G	p.Pro213Ala	missense_variant	Exon 4 of 5		NP_001193579.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PSG7	ENST00000406070.7	c.1003C>G	p.Pro335Ala	missense_variant	Exon 5 of 6	1	NM_002783.3	ENSP00000421986.1
PSG7	ENST00000623675.3	c.637C>G	p.Pro213Ala	missense_variant	Exon 4 of 5	1		ENSP00000485117.1
PSG7	ENST00000446844.3	c.1003C>G	p.Pro335Ala	missense_variant	Exon 5 of 5	5		ENSP00000470856.1
PSG7	ENST00000599226.2	n.1565C>G		non_coding_transcript_exon_variant	Exon 1 of 2	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Benign	0.0020	T
BayesDel_noAF	Benign	-0.23
CADD	Benign	18
DANN	Benign	0.94
DEOGEN2	Benign	0.11	T;.;.
FATHMM_MKL	Benign	0.0059	N
LIST_S2	Uncertain	0.96	D;D;D
MetaRNN	Benign	0.13	T;T;T
PhyloP100		0.21
PrimateAI	Benign	0.32	T
Sift4G	Benign	0.14	T;T;T
Polyphen		0.99	D;.;.
Vest4		0.21
MVP		0.12
GERP RS		-0.20
Varity_R		0.043
gMVP		0.039
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.22		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.22		Position offset: 14

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1205049115; hg19: chr19-43430165;