chr16-72076477-T-C

Position:

• chr16-72076477-T-C

Variant summary

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

The NM_020995.4(HPR):​c.443T>C​(p.Leu148Pro) 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. 14/21 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: HPR NM_020995.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.678

Genes affected

HPR (HGNC:5156): (haptoglobin-related protein) This gene encodes a haptoglobin-related protein that binds hemoglobin as efficiently as haptoglobin. Unlike haptoglobin, plasma concentration of this protein is unaffected in patients with sickle cell anemia and extensive intravascular hemolysis, suggesting a difference in binding between haptoglobin-hemoglobin and haptoglobin-related protein-hemoglobin complexes to CD163, the hemoglobin scavenger receptor. This protein may also be a clinically important predictor of recurrence of breast cancer. [provided by RefSeq, Oct 2011]

TXNL4B (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=0.19722241).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HPR	NM_020995.4	c.443T>C	p.Leu148Pro	missense_variant	5/5	ENST00000540303.7	NP_066275.3
HPR	NM_001384360.1	c.83T>C	p.Leu28Pro	missense_variant	6/6		NP_001371289.1
HPR	XM_024450251.2	c.461T>C	p.Leu154Pro	missense_variant	5/5		XP_024306019.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HPR	ENST00000540303.7	c.443T>C	p.Leu148Pro	missense_variant	5/5	1	NM_020995.4	ENSP00000441828.2
TXNL4B	ENST00000562153.5	c.284+12510A>G		intron_variant		4		ENSP00000454635.2

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

Jan 23, 2024

The c.443T>C (p.L148P) alteration is located in exon 5 (coding exon 5) of the HPR gene. This alteration results from a T to C substitution at nucleotide position 443, causing the leucine (L) at amino acid position 148 to be replaced by a proline (P). 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	Uncertain	0.55
BayesDel_addAF	Benign	-0.012	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	20
DANN	Benign	0.89
DEOGEN2	Benign	0.15	T;T
Eigen	Benign	-0.26
Eigen_PC	Benign	-0.41
FATHMM_MKL	Benign	0.66	D
LIST_S2	Benign	0.85	T;T
M_CAP	Benign	0.060	D
MetaRNN	Benign	0.20	T;T
MetaSVM	Uncertain	0.17	D
MutationAssessor	Benign	0.97	L;.
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-0.16	N;.
REVEL	Uncertain	0.41
Sift	Benign	0.23	T;.
Sift4G	Uncertain	0.011	D;D
Polyphen		1.0	D;.
Vest4		0.22
MutPred		0.50		Gain of disorder (P = 0.0142);.;
MVP		0.82
MPC		0.62
ClinPred		0.28	T
GERP RS		1.3
Varity_R		0.22
gMVP		0.70

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: chr16-72110376;