5-34796010-C-T

Variant names:

• chr5-34796010-C-T
• rs369411268
• NM_015577.3:c.239C>T

Variant summary

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

The NM_015577.3(RAI14):​c.239C>T​(p.Thr80Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,459,806 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. T80R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: RAI14 NM_015577.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.08
• Publications: 0 publications found

Genes affected

RAI14 (HGNC:14873): (retinoic acid induced 14) Predicted to enable actin binding activity. Predicted to be involved in several processes, including apoptotic signaling pathway; regulation of NIK/NF-kappaB signaling; and spermatogenesis. Located in cytosol; fibrillar center; and nucleoplasm. [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_015577.3. 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
	RAI14	NM_015577.3	MANE Select	c.239C>T	p.Thr80Ile	missense	Exon 4 of 18	NP_056392.2	Q9P0K7-1
	RAI14	NM_001145525.2		c.248C>T	p.Thr83Ile	missense	Exon 6 of 20	NP_001138997.1	Q9P0K7-2
	RAI14	NM_001145520.1		c.239C>T	p.Thr80Ile	missense	Exon 4 of 18	NP_001138992.1	Q9P0K7-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAI14	ENST00000265109.8	TSL:1 MANE Select	c.239C>T	p.Thr80Ile	missense	Exon 4 of 18	ENSP00000265109.3	Q9P0K7-1
	RAI14	ENST00000515799.5	TSL:1	c.248C>T	p.Thr83Ile	missense	Exon 6 of 20	ENSP00000427123.1	Q9P0K7-2
	RAI14	ENST00000428746.6	TSL:1	c.239C>T	p.Thr80Ile	missense	Exon 4 of 18	ENSP00000388725.2	Q9P0K7-1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1459806 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 726094

African (AFR) AF: 0.00 AC: 0 AN: 33462

American (AMR) AF: 0.00 AC: 0 AN: 44702

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26104

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39660

South Asian (SAS) AF: 0.00 AC: 0 AN: 86106

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53392

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5758

European-Non Finnish (NFE) AF: 9.01e-7 AC: 1 AN: 1110318

Other (OTH) AF: 0.00 AC: 0 AN: 60304

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.010
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.12	T
Eigen	Pathogenic	0.68
Eigen_PC	Pathogenic	0.73
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.86	D
M_CAP	Benign	0.028	D
MetaRNN	Uncertain	0.66	D
MetaSVM	Benign	-0.44	T
MutationAssessor	Benign	1.3	L
PhyloP100		5.1
PrimateAI	Uncertain	0.68	T
PROVEAN	Uncertain	-3.0	D
REVEL	Benign	0.28
Sift	Uncertain	0.0030	D
Sift4G	Benign	0.070	T
Polyphen		0.99	D
Vest4		0.60
MutPred		0.58		Loss of phosphorylation at T80 (P = 0.0444)
MVP		0.71
MPC		0.65
ClinPred		0.91	D
GERP RS		6.1
Varity_R		0.28
gMVP		0.22
Mutation Taster		=60/40	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs369411268; hg19: chr5-34796115;