rs142274487

Variant names:

• chr2-36981591-C-A
• rs142274487
• NM_019024.3:c.6115G>T

Your query was ambiguous. Multiple possible variants found:

• chr2-36981591-C-A
• chr2-36981591-C-G
• chr2-36981591-C-T

Variant summary

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

The NM_019024.3(HEATR5B):​c.6115G>T​(p.Val2039Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V2039I) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: HEATR5B NM_019024.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.00
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_019024.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HEATR5B	NM_019024.3	MANE Select	c.6115G>T	p.Val2039Phe	missense	Exon 36 of 36	NP_061897.1	Q9P2D3-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HEATR5B	ENST00000233099.6	TSL:1 MANE Select	c.6115G>T	p.Val2039Phe	missense	Exon 36 of 36	ENSP00000233099.5	Q9P2D3-1
	HEATR5B	ENST00000903982.1		c.6115G>T	p.Val2039Phe	missense	Exon 36 of 36	ENSP00000574041.1
	HEATR5B	ENST00000920714.1		c.6115G>T	p.Val2039Phe	missense	Exon 36 of 36	ENSP00000590773.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.84
BayesDel_addAF	Pathogenic	0.23	D
BayesDel_noAF	Uncertain	0.10
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.22	T
Eigen	Uncertain	0.47
Eigen_PC	Uncertain	0.54
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.017	T
MetaRNN	Uncertain	0.65	D
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	1.5	L
PhyloP100		3.0
PrimateAI	Uncertain	0.55	T
PROVEAN	Uncertain	-3.6	D
REVEL	Benign	0.24
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0020	D
Polyphen		0.93	P
Vest4		0.80
MutPred		0.46		Loss of MoRF binding (P = 0.0898)
MVP		0.63
MPC		0.33
ClinPred		0.99	D
GERP RS		5.6
Varity_R		0.63
gMVP		0.83
Mutation Taster		=73/27	polymorphism

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

Other links and lift over

dbSNP: rs142274487; hg19: chr2-37208734;