5-34796010-C-T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 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

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAI14	NM_015577.3	c.239C>T	p.Thr80Ile	missense_variant	Exon 4 of 18	ENST00000265109.8	NP_056392.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAI14	ENST00000265109.8	c.239C>T	p.Thr80Ile	missense_variant	Exon 4 of 18	1	NM_015577.3	ENSP00000265109.3

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

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.01e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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;T;.;.;T;.;T;T;T;T;.;.;.;.
Eigen	Pathogenic	0.68
Eigen_PC	Pathogenic	0.73
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.86	.;D;.;D;.;D;D;D;D;D;T;D;D;D
M_CAP	Benign	0.028	D
MetaRNN	Uncertain	0.66	D;D;D;D;D;D;D;D;D;D;D;D;D;D
MetaSVM	Benign	-0.44	T
MutationAssessor	Benign	1.3	L;.;.;L;L;.;L;.;.;.;.;.;.;.
PrimateAI	Uncertain	0.68	T
PROVEAN	Uncertain	-3.0	D;D;D;D;D;D;D;D;D;D;D;D;D;D
REVEL	Benign	0.28
Sift	Uncertain	0.0030	D;D;D;D;D;D;D;D;D;D;D;D;D;D
Sift4G	Benign	0.070	T;T;T;T;T;T;T;T;T;T;T;T;D;T
Polyphen		0.99	D;.;.;.;D;.;D;.;.;.;D;.;.;D
Vest4		0.60
MutPred		0.58		Loss of phosphorylation at T80 (P = 0.0444);Loss of phosphorylation at T80 (P = 0.0444);Loss of phosphorylation at T80 (P = 0.0444);Loss of phosphorylation at T80 (P = 0.0444);Loss of phosphorylation at T80 (P = 0.0444);Loss of phosphorylation at T80 (P = 0.0444);Loss of phosphorylation at T80 (P = 0.0444);Loss of phosphorylation at T80 (P = 0.0444);Loss of phosphorylation at T80 (P = 0.0444);Loss of phosphorylation at T80 (P = 0.0444);.;Loss of phosphorylation at T80 (P = 0.0444);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

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-34796115;