2-36990686-T-A

Position:

• chr2-36990686-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_019024.3(HEATR5B):​c.5659A>T​(p.Asn1887Tyr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: HEATR5B NM_019024.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.13

Genes affected

HEATR5B (HGNC:29273): (HEAT repeat containing 5B) Predicted to be involved in endocytosis; protein localization; and retrograde transport, endosome to Golgi. Located in membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.30404735).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HEATR5B	NM_019024.3	c.5659A>T	p.Asn1887Tyr	missense_variant	34/36	ENST00000233099.6	NP_061897.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HEATR5B	ENST00000233099.6	c.5659A>T	p.Asn1887Tyr	missense_variant	34/36	1	NM_019024.3	ENSP00000233099.5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

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

Jun 26, 2024

The c.5659A>T (p.N1887Y) alteration is located in exon 34 (coding exon 33) of the HEATR5B gene. This alteration results from a A to T substitution at nucleotide position 5659, causing the asparagine (N) at amino acid position 1887 to be replaced by a tyrosine (Y). 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	0.090
BayesDel_addAF	Benign	-0.068	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.22	T
Eigen	Benign	-0.011
Eigen_PC	Benign	0.11
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.037	D
MetaRNN	Benign	0.30	T
MetaSVM	Benign	-0.83	T
MutationAssessor	Benign	1.6	L
PrimateAI	Benign	0.35	T
PROVEAN	Pathogenic	-5.6	D
REVEL	Benign	0.17
Sift	Uncertain	0.021	D
Sift4G	Uncertain	0.030	D
Polyphen		0.22	B
Vest4		0.31
MutPred		0.43		Gain of catalytic residue at N1887 (P = 0.0337);
MVP		0.51
MPC		0.18
ClinPred		0.99	D
GERP RS		4.3
Varity_R		0.39
gMVP		0.48

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: chr2-37217829;