4-73438203-A-G

Position:

• chr4-73438203-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001134.3(AFP):​c.167A>G​(p.Gln56Arg) 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. 12/21 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: AFP NM_001134.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.207

Genes affected

AFP (HGNC:317): (alpha fetoprotein) This gene encodes alpha-fetoprotein, a major plasma protein produced by the yolk sac and the liver during fetal life. Alpha-fetoprotein expression in adults is often associated with hepatocarcinoma and with teratoma, and has prognostic value for managing advanced gastric cancer. However, hereditary persistance of alpha-fetoprotein may also be found in individuals with no obvious pathology. The protein is thought to be the fetal counterpart of serum albumin, and the alpha-fetoprotein and albumin genes are present in tandem in the same transcriptional orientation on chromosome 4. Alpha-fetoprotein is found in monomeric as well as dimeric and trimeric forms, and binds copper, nickel, fatty acids and bilirubin. The level of alpha-fetoprotein in amniotic fluid is used to measure renal loss of protein to screen for spina bifida and anencephaly. [provided by RefSeq, Oct 2019]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2763241).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AFP	NM_001134.3	c.167A>G	p.Gln56Arg	missense_variant	3/15	ENST00000395792.7
AFP	NM_001354717.2	c.-166A>G		5_prime_UTR_variant	3/16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AFP	ENST00000395792.7	c.167A>G	p.Gln56Arg	missense_variant	3/15	1	NM_001134.3	P1
AFP	ENST00000226359.2	c.167A>G	p.Gln56Arg	missense_variant	3/14	5

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	0.13
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.34	T;T
Eigen	Benign	-0.53
Eigen_PC	Benign	-0.64
FATHMM_MKL	Benign	0.51	D
LIST_S2	Benign	0.67	T;T
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.28	T;T
MetaSVM	Benign	-0.86	T
MutationAssessor	Pathogenic	3.0	M;.
MutationTaster	Benign	0.99	N;N
PrimateAI	Benign	0.33	T
PROVEAN	Uncertain	-3.4	D;D
REVEL	Benign	0.13
Sift	Uncertain	0.016	D;D
Sift4G	Uncertain	0.029	D;D
Polyphen		0.27	B;.
Vest4		0.41
MutPred		0.65		Gain of glycosylation at Y60 (P = 0.0568);Gain of glycosylation at Y60 (P = 0.0568);
MVP		0.57
MPC		0.10
ClinPred		0.56	D
GERP RS		-0.77
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.45
gMVP		0.46

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: chr4-74303920;