16-72057415-A-G

Position:

• chr16-72057415-A-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4 BP6

The NM_005143.5(HP):​c.214A>G​(p.Lys72Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency: Genomes: not found (cov: 19)
• Consequence: HP NM_005143.5 missense
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 2.37

Genes affected

HP (HGNC:5141): (haptoglobin) This gene encodes a preproprotein, which is processed to yield both alpha and beta chains, which subsequently combine as a tetramer to produce haptoglobin. Haptoglobin functions to bind free plasma hemoglobin, which allows degradative enzymes to gain access to the hemoglobin, while at the same time preventing loss of iron through the kidneys and protecting the kidneys from damage by hemoglobin. Mutations in this gene and/or its regulatory regions cause ahaptoglobinemia or hypohaptoglobinemia. This gene has also been linked to diabetic nephropathy, the incidence of coronary artery disease in type 1 diabetes, Crohn's disease, inflammatory disease behavior, primary sclerosing cholangitis, susceptibility to idiopathic Parkinson's disease, and a reduced incidence of Plasmodium falciparum malaria. The protein encoded also exhibits antimicrobial activity against bacteria. A similar duplicated gene is located next to this gene on chromosome 16. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2014]

TXNL4B (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.2689277).
• BP6: Variant 16-72057415-A-G is Benign according to our data. Variant chr16-72057415-A-G is described in ClinVar as [Benign]. Clinvar id is 15898.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HP	NM_005143.5	c.214A>G	p.Lys72Glu	missense_variant	4/7	ENST00000355906.10	NP_005134.1
HP	NM_001318138.2	c.214A>G	p.Lys72Glu	missense_variant	4/5		NP_001305067.1
HP	NM_001126102.3	c.190+784A>G		intron_variant			NP_001119574.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HP	ENST00000355906.10	c.214A>G	p.Lys72Glu	missense_variant	4/7	1	NM_005143.5	ENSP00000348170.5
TXNL4B	ENST00000562153.5	c.285-13058T>C		intron_variant		4		ENSP00000454635.2

Frequencies

GnomAD3 genomes Cov.: 19

GnomAD4 exome Cov.: 14

GnomAD4 genome Cov.: 19

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

HAPTOGLOBIN, ALPHA-1, FAST-SLOW POLYMORPHISM Benign:1

Benign, no assertion criteria provided

literature only

OMIM

Oct 01, 1983

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.090	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	17
DANN	Benign	0.57
DEOGEN2	Benign	0.29	T;.;.
Eigen	Benign	0.17
Eigen_PC	Benign	0.045
FATHMM_MKL	Benign	0.68	D
LIST_S2	Uncertain	0.91	D;D;D
M_CAP	Benign	0.050	D
MetaRNN	Benign	0.27	T;T;T
MetaSVM	Benign	-0.75	T
MutationAssessor	Pathogenic	3.0	M;.;.
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	-0.22	N;.;N
REVEL	Benign	0.14
Sift	Benign	0.39	T;.;T
Sift4G	Pathogenic	0.0	D;D;D
Polyphen		0.98	D;.;.
Vest4		0.37
MutPred		0.49		Loss of ubiquitination at K72 (P = 0.0244);Loss of ubiquitination at K72 (P = 0.0244);Loss of ubiquitination at K72 (P = 0.0244);
MVP		0.57
MPC		0.39
ClinPred		0.41	T
GERP RS		3.2
Varity_R		0.13
gMVP		0.46

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs137853233; hg19: chr16-72091314;