rs78953271

Variant names:

• chr4-73413606-G-A
• rs78953271
• NM_000477.7:c.1030G>A

Variant summary

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

The NM_000477.7(ALB):​c.1030G>A​(p.Ala344Thr) 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. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as no classification for the single variant (no stars).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ALB NM_000477.7 missense
• Clinical Significance: no classification for the single variant no classification for the single variant O:1
• Conservation: PhyloP100: -0.451
• Publications: 5 publications found

Genes affected

ALB (HGNC:399): (albumin) This gene encodes the most abundant protein in human blood. This protein functions in the regulation of blood plasma colloid osmotic pressure and acts as a carrier protein for a wide range of endogenous molecules including hormones, fatty acids, and metabolites, as well as exogenous drugs. Additionally, this protein exhibits an esterase-like activity with broad substrate specificity. The encoded preproprotein is proteolytically processed to generate the mature protein. A peptide derived from this protein, EPI-X4, is an endogenous inhibitor of the CXCR4 chemokine receptor. [provided by RefSeq, Jul 2016]

ALB Gene-Disease associations (from GenCC):

• congenital analbuminemia

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics
• hyperthyroxinemia, familial dysalbuminemic

  Inheritance: AD Classification: STRONG, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

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=0.17818841).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALB	NM_000477.7	c.1030G>A	p.Ala344Thr	missense_variant	Exon 8 of 15	ENST00000295897.9	NP_000468.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALB	ENST00000295897.9	c.1030G>A	p.Ala344Thr	missense_variant	Exon 8 of 15	1	NM_000477.7	ENSP00000295897.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Significance: no classification for the single variant

Submissions summary: Other:1

Revision: no classification for the single variant

Submissions by phenotype

ALBUMIN REDHILL Other:1

Jul 18, 2019

OMIM

Significance: other

Review Status: no assertion criteria provided

Collection Method: literature only

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.069
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	10
DANN	Benign	0.94
DEOGEN2	Benign	0.23	T;.;.;.;T
Eigen	Benign	-0.63
Eigen_PC	Benign	-0.79
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.71	T;T;T;T;T
M_CAP	Benign	0.031	D
MetaRNN	Benign	0.18	T;T;T;T;T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	1.3	L;.;.;.;.
PhyloP100		-0.45
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-1.0	N;N;N;N;N
REVEL	Benign	0.17
Sift	Benign	0.078	T;T;T;T;T
Sift4G	Benign	0.12	T;T;T;T;T
Polyphen		0.018	B;B;B;.;B
Vest4		0.062
MutPred		0.34		Gain of phosphorylation at A344 (P = 0.0768);.;.;Gain of phosphorylation at A344 (P = 0.0768);.;
MVP		0.69
MPC		0.21
ClinPred		0.083	T
GERP RS		-4.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.23
gMVP		0.12
Mutation Taster		=75/25	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.14		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: rs78953271; hg19: chr4-74279323;