3-186613258-A-C

Position:

• chr3-186613258-A-C

Variant summary

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

The NM_001622.4(AHSG):​c.117A>C​(p.Glu39Asp) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: AHSG NM_001622.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.00100

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]

AHSG (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=0.07798749).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AHSG	NM_001622.4	c.117A>C	p.Glu39Asp	missense_variant	1/7	ENST00000411641.7	NP_001613.2
AHSG	NM_001354571.2	c.117A>C	p.Glu39Asp	missense_variant	1/7		NP_001341500.1
AHSG	NM_001354572.2	c.117A>C	p.Glu39Asp	missense_variant	1/7		NP_001341501.1
AHSG	NM_001354573.2	c.117A>C	p.Glu39Asp	missense_variant	1/6		NP_001341502.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AHSG	ENST00000411641.7	c.117A>C	p.Glu39Asp	missense_variant	1/7	1	NM_001622.4	ENSP00000393887.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

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

Dec 09, 2023

The c.117A>C (p.E39D) alteration is located in exon 1 (coding exon 1) of the AHSG gene. This alteration results from a A to C substitution at nucleotide position 117, causing the glutamic acid (E) at amino acid position 39 to be replaced by an aspartic acid (D). 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	0.20
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	16
DANN	Benign	0.95
DEOGEN2	Benign	0.19	T;T
Eigen	Benign	-0.83
Eigen_PC	Benign	-0.78
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.72	T;T
M_CAP	Benign	0.0055	T
MetaRNN	Benign	0.078	T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.94	L;.
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-1.0	N;N
REVEL	Benign	0.032
Sift	Benign	0.52	T;T
Sift4G	Benign	0.52	T;T
Polyphen		0.0070	B;B
Vest4		0.16
MutPred		0.33		Gain of phosphorylation at T37 (P = 0.1654);Gain of phosphorylation at T37 (P = 0.1654);
MVP		0.31
MPC		0.078
ClinPred		0.24	T
GERP RS		-3.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Varity_R		0.081
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

LitVar

Other links and lift over

dbSNP: rs1246111953; hg19: chr3-186331047;