6-144095379-T-A

Variant names:

• chr6-144095379-T-A
• rs375478384
• NM_031287.3:c.119A>T

Variant summary

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

The NM_031287.3(SF3B5):​c.119A>T​(p.Tyr40Phe) variant causes a missense change involving the alteration of a 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: SF3B5 NM_031287.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.95
• Publications: 0 publications found

Genes affected

SF3B5 (HGNC:21083): (splicing factor 3b subunit 5) Enables RNA binding activity and splicing factor binding activity. Involved in mRNA splicing, via spliceosome. Located in nucleoplasm. Part of U12-type spliceosomal complex and U2-type precatalytic spliceosome. [provided by Alliance of Genome Resources, Apr 2022]

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=0.3730489).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031287.3. 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
	SF3B5	NM_031287.3	MANE Select	c.119A>T	p.Tyr40Phe	missense	Exon 1 of 1	NP_112577.1	Q9BWJ5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SF3B5	ENST00000367569.4	TSL:6 MANE Select	c.119A>T	p.Tyr40Phe	missense	Exon 1 of 1	ENSP00000356541.2	Q9BWJ5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

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	0.056
BayesDel_addAF	Uncertain	0.071	D
BayesDel_noAF	Benign	-0.14
CADD	Uncertain	24
DANN	Uncertain	0.98
DEOGEN2	Benign	0.074	T
Eigen	Benign	0.15
Eigen_PC	Uncertain	0.35
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Benign	0.070	D
MetaRNN	Benign	0.37	T
MetaSVM	Benign	-1.0	T
PhyloP100		7.9
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.13
Sift	Benign	0.093	T
Sift4G	Benign	0.25	T
Polyphen		0.0010	B
Vest4		0.61
MutPred		0.62		Gain of helix (P = 0.1736)
MVP		0.46
MPC		1.0
ClinPred		0.99	D
GERP RS		6.1
PromoterAI		0.043	Neutral
Varity_R		0.72
gMVP		0.87
Mutation Taster		=36/64	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs375478384; hg19: chr6-144416516;