3-186620593-G-A

Variant names:

• chr3-186620593-G-A
• rs4918
• NM_001622.4:c.767G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001622.4(AHSG):​c.767G>A​(p.Ser256Asn) 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. 15/21 in silico tools predict 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. S256T) has been classified as Benign.

• Frequency: Genomes: not found (cov: 31)
• Consequence: AHSG NM_001622.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.591
• Publications: 87 publications found

Genes affected

AHSG (HGNC:349): (alpha 2-HS glycoprotein) The protein encoded by this gene is a negatively-charged serum glycoprotein that is synthesized by hepatocytes. The encoded protein consists of two polypeptide chains, which are both cleaved from a proprotein encoded from a single mRNA. It is involved in several processes, including endocytosis, brain development, and the formation of bone tissue. Defects in this gene are a cause of susceptibility to leanness. [provided by RefSeq, Aug 2017]

HRG-AS1 (HGNC:55915): (HRG and FETUB antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06969914).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001622.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AHSG	NM_001622.4	MANE Select	c.767G>A	p.Ser256Asn	missense	Exon 7 of 7	NP_001613.2
	AHSG	NM_001354571.2		c.770G>A	p.Ser257Asn	missense	Exon 7 of 7	NP_001341500.1
	AHSG	NM_001354572.2		c.764G>A	p.Ser255Asn	missense	Exon 7 of 7	NP_001341501.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AHSG	ENST00000411641.7	TSL:1 MANE Select	c.767G>A	p.Ser256Asn	missense	Exon 7 of 7	ENSP00000393887.2
	AHSG	ENST00000273784.5	TSL:3	c.770G>A	p.Ser257Asn	missense	Exon 7 of 7	ENSP00000273784.5
	HRG-AS1	ENST00000625386.2	TSL:5	n.388+21361C>T		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 44

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.095
BayesDel_addAF	Benign	-0.45	T
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.41
DANN	Benign	0.90
DEOGEN2	Benign	0.0097	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.058	N
LIST_S2	Benign	0.24	T
M_CAP	Benign	0.0038	T
MetaRNN	Benign	0.070	T
MetaSVM	Benign	-0.96	T
PhyloP100		-0.59
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.67	N
REVEL	Benign	0.012
Sift	Benign	0.096	T
Sift4G	Benign	0.22	T
Polyphen		0.0020	B
Vest4		0.086
MutPred		0.26		Loss of glycosylation at S257 (P = 0.0289)
MVP		0.18
MPC		0.077
ClinPred		0.088	T
GERP RS		-3.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.042
gMVP		0.12
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs4918; hg19: chr3-186338382;