chr5-34812192-C-T

Variant names:

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

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>T​(p.Pro250Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000699 in 1,429,832 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: not found (cov: 33)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: RAI14 NM_015577.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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=0.19057894).

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>T	p.Pro250Leu	missense	Exon 10 of 18	NP_056392.2	Q9P0K7-1
	RAI14	NM_001145525.2		c.758C>T	p.Pro253Leu	missense	Exon 12 of 20	NP_001138997.1	Q9P0K7-2
	RAI14	NM_001145520.1		c.749C>T	p.Pro250Leu	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>T	p.Pro250Leu	missense	Exon 10 of 18	ENSP00000265109.3	Q9P0K7-1
	RAI14	ENST00000515799.5	TSL:1	c.758C>T	p.Pro253Leu	missense	Exon 12 of 20	ENSP00000427123.1	Q9P0K7-2
	RAI14	ENST00000428746.6	TSL:1	c.749C>T	p.Pro250Leu	missense	Exon 10 of 18	ENSP00000388725.2	Q9P0K7-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.99e-7 AC: 1 AN: 1429832 Hom.: 0 Cov.: 30 AF XY: 0.00000140 AC XY: 1 AN XY: 712504

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

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

American (AMR) AF: 0.00 AC: 0 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: 0.0000120 AC: 1 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: 0.00 AC: 0 AN: 1087884

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

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.098	T
BayesDel_noAF	Benign	-0.38
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.033	T
Eigen	Benign	0.054
Eigen_PC	Uncertain	0.23
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	2.0	M
PhyloP100		3.2
PrimateAI	Uncertain	0.58	T
PROVEAN	Uncertain	-3.3	D
REVEL	Benign	0.060
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.0030	D
Polyphen		0.0	B
Vest4		0.14
MutPred		0.20		Loss of glycosylation at P250 (P = 0.0336)
MVP		0.50
MPC		0.16
ClinPred		0.83	D
GERP RS		5.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.16
gMVP		0.38
Mutation Taster		=83/17	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.18		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;