12-45923075-G-T

Variant names:

• chr12-45923075-G-T
• rs202135977
• NM_004719.3:c.3986C>A

Variant summary

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

The NM_004719.3(SCAF11):​c.3986C>A​(p.Thr1329Lys) 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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SCAF11 NM_004719.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0690

Genes affected

SCAF11 (HGNC:10784): (SR-related CTD associated factor 11) Enables RNA binding activity. Involved in spliceosomal complex assembly. Located in nuclear body and nucleolus. [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=0.11946663).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCAF11	NM_004719.3	c.3986C>A	p.Thr1329Lys	missense_variant	Exon 13 of 15	ENST00000369367.8	NP_004710.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCAF11	ENST00000369367.8	c.3986C>A	p.Thr1329Lys	missense_variant	Exon 13 of 15	1	NM_004719.3	ENSP00000358374.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	5.5
DANN	Benign	0.82
DEOGEN2	Benign	0.021	T;.;T
Eigen	Benign	-0.87
Eigen_PC	Benign	-0.97
FATHMM_MKL	Benign	0.10	N
LIST_S2	Benign	0.83	T;T;T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.12	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L;.;.
PrimateAI	Benign	0.21	T
PROVEAN	Benign	-2.0	N;N;N
REVEL	Benign	0.088
Sift	Uncertain	0.023	D;D;D
Sift4G	Uncertain	0.049	D;T;T
Polyphen		0.59	P;.;.
Vest4		0.18
MutPred		0.33		Gain of ubiquitination at T1329 (P = 0.0066);.;.;
MVP		0.082
MPC		0.064
ClinPred		0.13	T
GERP RS		-3.8
Varity_R		0.072
gMVP		0.22

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

Publications

LitVar

Other links and lift over

dbSNP: rs202135977; hg19: chr12-46316858;