5-34812192-C-A

Variant names:

• chr5-34812192-C-A
• rs1294093591
• NM_015577.3:c.749C>A

Variant summary

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

The NM_015577.3(RAI14):​c.749C>A​(p.Pro250Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000014 in 1,429,832 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 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. P250L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: RAI14 NM_015577.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.15
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.22398782).

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.749C>A	p.Pro250Gln	missense	Exon 10 of 18	NP_056392.2	Q9P0K7-1
	RAI14	NM_001145525.2		c.758C>A	p.Pro253Gln	missense	Exon 12 of 20	NP_001138997.1	Q9P0K7-2
	RAI14	NM_001145520.1		c.749C>A	p.Pro250Gln	missense	Exon 10 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.749C>A	p.Pro250Gln	missense	Exon 10 of 18	ENSP00000265109.3	Q9P0K7-1
	RAI14	ENST00000515799.5	TSL:1	c.758C>A	p.Pro253Gln	missense	Exon 12 of 20	ENSP00000427123.1	Q9P0K7-2
	RAI14	ENST00000428746.6	TSL:1	c.749C>A	p.Pro250Gln	missense	Exon 10 of 18	ENSP00000388725.2	Q9P0K7-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000410 AC: 1 AN: 243716 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000895

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000140 AC: 2 AN: 1429832 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 712504

African (AFR) AF: 0.00 AC: 0 AN: 32246

American (AMR) AF: 0.0000233 AC: 1 AN: 42968

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25808

East Asian (EAS) AF: 0.00 AC: 0 AN: 39418

South Asian (SAS) AF: 0.00 AC: 0 AN: 83268

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53314

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5664

European-Non Finnish (NFE) AF: 9.19e-7 AC: 1 AN: 1087884

Other (OTH) AF: 0.00 AC: 0 AN: 59262

GnomAD4 genome Cov.: 33

Alfa AF: 0.000111 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.086	T
BayesDel_noAF	Benign	-0.36
CADD	Uncertain	24
DANN	Uncertain	0.98
DEOGEN2	Benign	0.029	T
Eigen	Uncertain	0.28
Eigen_PC	Uncertain	0.38
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	2.0	M
PhyloP100		3.2
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.057
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.015	D
Polyphen		0.18	B
Vest4		0.29
MutPred		0.23		Loss of glycosylation at P250 (P = 0.0336)
MVP		0.44
MPC		0.44
ClinPred		0.75	D
GERP RS		5.4
Varity_R		0.13
gMVP		0.37
Mutation Taster		=82/18	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.14		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: rs1294093591; hg19: chr5-34812297;