rs1461213136

Variant names:

• chr16-50066467-C-T
• rs1461213136
• NM_182922.4:c.239C>T

Variant summary

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

The NM_182922.4(HEATR3):​c.239C>T​(p.Ala80Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000516 in 1,355,848 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000033 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000017 (0 hom.)
• Consequence: HEATR3 NM_182922.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.14
• Publications: 1 publications found

Genes affected

HEATR3 (HGNC:26087): (HEAT repeat containing 3) The protein encoded by this gene plays a role in ribosomal protein transport and in the assembly of the 5S ribonucleoprotein particle (5S RNP). The encoded protein also may be involved in NOD2-mediated NF-kappaB signaling. [provided by RefSeq, Jul 2016]

HEATR3-AS1 (HGNC:55406): (HEATR3 antisense RNA 1)

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=0.13697687).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_182922.4. 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
	HEATR3	NM_182922.4	MANE Select	c.239C>T	p.Ala80Val	missense	Exon 2 of 15	NP_891552.1	Q7Z4Q2-1
	HEATR3	NM_001329729.2		c.-454C>T		5_prime_UTR	Exon 2 of 16	NP_001316658.1
	HEATR3	NM_001329730.2		c.-428C>T		5_prime_UTR	Exon 2 of 16	NP_001316659.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HEATR3	ENST00000299192.8	TSL:1 MANE Select	c.239C>T	p.Ala80Val	missense	Exon 2 of 15	ENSP00000299192.7	Q7Z4Q2-1
	HEATR3	ENST00000887924.1		c.239C>T	p.Ala80Val	missense	Exon 2 of 15	ENSP00000557983.1
	HEATR3	ENST00000887923.1		c.239C>T	p.Ala80Val	missense	Exon 2 of 14	ENSP00000557982.1

Frequencies

GnomAD3 genomes AF: 0.0000329 AC: 5 AN: 152152 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000965

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000166 AC: 2 AN: 1203696 Hom.: 0 Cov.: 33 AF XY: 0.00000172 AC XY: 1 AN XY: 582768

African (AFR) AF: 0.00 AC: 0 AN: 23764

American (AMR) AF: 0.000107 AC: 1 AN: 9326

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16624

East Asian (EAS) AF: 0.00 AC: 0 AN: 27326

South Asian (SAS) AF: 0.00 AC: 0 AN: 50118

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 28792

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4510

European-Non Finnish (NFE) AF: 0.00000101 AC: 1 AN: 993692

Other (OTH) AF: 0.00 AC: 0 AN: 49544

GnomAD4 genome AF: 0.0000329 AC: 5 AN: 152152 Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2 AN XY: 74326

African (AFR) AF: 0.0000965 AC: 4 AN: 41462

American (AMR) AF: 0.0000654 AC: 1 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4838

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10600

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67994

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.0000227

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Diamond-Blackfan anemia 21 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.049	T
BayesDel_noAF	Benign	-0.31
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.00091	T
Eigen	Benign	-0.25
Eigen_PC	Benign	-0.13
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Uncertain	0.86	D
M_CAP	Uncertain	0.23	D
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.2	L
PhyloP100		3.1
PrimateAI	Pathogenic	0.94	D
PROVEAN	Benign	0.63	N
REVEL	Benign	0.12
Sift	Benign	1.0	T
Sift4G	Benign	0.47	T
Polyphen		0.59	P
Vest4		0.15
MutPred		0.44		Loss of disorder (P = 0.0964)
MVP		0.41
MPC		0.27
ClinPred		0.78	D
GERP RS		4.5
PromoterAI		0.065	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.068
gMVP		0.31

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: rs1461213136; hg19: chr16-50100378;