5-34757584-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_015577.3(RAI14):c.153T>G(p.Ser51Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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)
• Consequence: RAI14 NM_015577.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.60

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14649281).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RAI14	NM_015577.3	c.153T>G	p.Ser51Arg	missense_variant	3/18	ENST00000265109.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RAI14	ENST00000265109.8	c.153T>G	p.Ser51Arg	missense_variant	3/18	1	NM_015577.3	P3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 23, 2023

The c.162T>G (p.S54R) alteration is located in exon 5 (coding exon 2) of the RAI14 gene. This alteration results from a T to G substitution at nucleotide position 162, causing the serine (S) at amino acid position 54 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.61
BayesDel_addAF	Benign	-0.056	T
BayesDel_noAF	Benign	-0.32
Cadd	Benign	19
Dann	Benign	0.61
DEOGEN2	Benign	0.024	T;T;.;.;T;.;T;T;T;T;.;.;.;.
Eigen	Benign	-0.88
Eigen_PC	Benign	-0.99
FATHMM_MKL	Benign	0.17	N
M_CAP	Uncertain	0.087	D
MetaRNN	Benign	0.15	T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.47	T
MutationTaster	Benign	0.97	D;D;D;D;D;D;D
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-2.2	N;D;D;N;N;D;N;D;D;D;N;D;D;N
REVEL	Benign	0.29
Sift	Uncertain	0.027	D;D;D;T;D;D;D;D;D;D;D;D;D;D
Sift4G	Benign	0.10	T;T;T;T;T;T;T;T;T;T;T;T;T;D
Polyphen		1.0	D;.;.;.;D;.;D;.;.;.;D;.;.;P
Vest4		0.39
MutPred		0.31		Gain of MoRF binding (P = 0.0166);Gain of MoRF binding (P = 0.0166);Gain of MoRF binding (P = 0.0166);Gain of MoRF binding (P = 0.0166);Gain of MoRF binding (P = 0.0166);Gain of MoRF binding (P = 0.0166);Gain of MoRF binding (P = 0.0166);Gain of MoRF binding (P = 0.0166);Gain of MoRF binding (P = 0.0166);Gain of MoRF binding (P = 0.0166);.;Gain of MoRF binding (P = 0.0166);Gain of MoRF binding (P = 0.0166);.;
MVP		0.41
MPC		0.45
ClinPred		0.40	T
GERP RS		-3.8
Varity_R		0.17
gMVP		0.36

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: chr5-34757689;