10-119576739-A-C

Variant names:

• chr10-119576739-A-C
• NM_003252.4:c.873T>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_003252.4(TIAL1):​c.873T>G​(p.Ser291Arg) 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. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TIAL1 NM_003252.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.99
• Publications: 0 publications found

Genes affected

TIAL1 (HGNC:11804): (TIA1 cytotoxic granule associated RNA binding protein like 1) The protein encoded by this gene is a member of a family of RNA-binding proteins, has three RNA recognition motifs (RRMs), and binds adenine and uridine-rich elements in mRNA and pre-mRNAs of a wide range of genes. It regulates various activities including translational control, splicing and apoptosis. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. The different isoforms have been show to function differently with respect to post-transcriptional silencing. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.32736582).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003252.4. 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
	TIAL1	NM_003252.4	MANE Select	c.873T>G	p.Ser291Arg	missense	Exon 11 of 12	NP_003243.1	Q01085-1
	TIAL1	NM_001033925.2		c.924T>G	p.Ser308Arg	missense	Exon 11 of 12	NP_001029097.1	Q01085-2
	TIAL1	NM_001323968.2		c.807T>G	p.Ser269Arg	missense	Exon 12 of 13	NP_001310897.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TIAL1	ENST00000436547.7	TSL:1 MANE Select	c.873T>G	p.Ser291Arg	missense	Exon 11 of 12	ENSP00000394902.2	Q01085-1
	TIAL1	ENST00000497671.5	TSL:1	n.*841T>G		non_coding_transcript_exon	Exon 12 of 13	ENSP00000431009.1	E7ETC0
	TIAL1	ENST00000497671.5	TSL:1	n.*841T>G		3_prime_UTR	Exon 12 of 13	ENSP00000431009.1	E7ETC0

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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	Pathogenic	0.75
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.35	T
Eigen	Benign	-0.41
Eigen_PC	Benign	-0.28
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.97	D
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.33	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.4	L
PhyloP100		2.0
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.11
Sift	Benign	0.34	T
Sift4G	Benign	0.51	T
Polyphen		0.0	B
Vest4		0.60
MutPred		0.43		Gain of MoRF binding (P = 0.0065)
MVP		0.44
MPC		1.6
ClinPred		0.16	T
GERP RS		1.9
Varity_R		0.049
gMVP		0.90
Mutation Taster		=43/56	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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

hg19: chr10-121336251;