rs7315731

chr12-45927731-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004719.3(SCAF11):c.1970T>A(p.Phe657Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.474 in 1,609,834 control chromosomes in the GnomAD database, including 186,367 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.39 (13529 hom., cov: 31)
  • Exomes 𝑓: 0.48 (172838 hom.)
• Consequence: SCAF11 NM_004719.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00600

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=7.763106E-5).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.529 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SCAF11	NM_004719.3	c.1970T>A	p.Phe657Tyr	missense_variant	11/15	ENST00000369367.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SCAF11	ENST00000369367.8	c.1970T>A	p.Phe657Tyr	missense_variant	11/15	1	NM_004719.3	P1
SCAF11	ENST00000549162.5	c.1394T>A	p.Phe465Tyr	missense_variant	5/9	1
SCAF11	ENST00000465950.5	c.1025T>A	p.Phe342Tyr	missense_variant	1/5	1
SCAF11	ENST00000547018.5	c.1790T>A	p.Phe597Tyr	missense_variant	11/11	5

Frequencies

GnomAD3 genomes AF: 0.393 AC: 59706 AN: 151870 Hom.: 13514 Cov.: 31

Gnomad AFR AF: 0.154

Gnomad AMI AF: 0.525

Gnomad AMR AF: 0.397

Gnomad ASJ AF: 0.518

Gnomad EAS AF: 0.544

Gnomad SAS AF: 0.515

Gnomad FIN AF: 0.521

Gnomad MID AF: 0.513

Gnomad NFE AF: 0.489

Gnomad OTH AF: 0.403

GnomAD3 exomes AF: 0.463 AC: 115218 AN: 248810 Hom.: 27740 AF XY: 0.474 AC XY: 63727 AN XY: 134578

Gnomad AFR exome AF: 0.146

Gnomad AMR exome AF: 0.413

Gnomad ASJ exome AF: 0.519

Gnomad EAS exome AF: 0.548

Gnomad SAS exome AF: 0.516

Gnomad FIN exome AF: 0.512

Gnomad NFE exome AF: 0.481

Gnomad OTH exome AF: 0.461

GnomAD4 exome AF: 0.483 AC: 704063 AN: 1457846 Hom.: 172838 Cov.: 38 AF XY: 0.486 AC XY: 352131 AN XY: 725250

Gnomad4 AFR exome AF: 0.146

Gnomad4 AMR exome AF: 0.409

Gnomad4 ASJ exome AF: 0.524

Gnomad4 EAS exome AF: 0.477

Gnomad4 SAS exome AF: 0.520

Gnomad4 FIN exome AF: 0.499

Gnomad4 NFE exome AF: 0.492

Gnomad4 OTH exome AF: 0.472

GnomAD4 genome AF: 0.393 AC: 59732 AN: 151988 Hom.: 13529 Cov.: 31 AF XY: 0.397 AC XY: 29477 AN XY: 74276

Gnomad4 AFR AF: 0.154

Gnomad4 AMR AF: 0.397

Gnomad4 ASJ AF: 0.518

Gnomad4 EAS AF: 0.546

Gnomad4 SAS AF: 0.517

Gnomad4 FIN AF: 0.521

Gnomad4 NFE AF: 0.489

Gnomad4 OTH AF: 0.408

Alfa AF: 0.479 Hom.: 13744

Bravo AF: 0.375

TwinsUK AF: 0.499 AC: 1850

ALSPAC AF: 0.489 AC: 1883

ESP6500AA AF: 0.165 AC: 729

ESP6500EA AF: 0.504 AC: 4337

ExAC AF: 0.456 AC: 55382

Asia WGS AF: 0.466 AC: 1618 AN: 3472

EpiCase AF: 0.485

EpiControl AF: 0.484

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.074
BayesDel_addAF	Benign	-0.68	T
BayesDel_noAF	Benign	-0.61
Cadd	Benign	0.84
Dann	Benign	0.95
DEOGEN2	Benign	0.027	T;.;T
Eigen	Benign	-0.59
Eigen_PC	Benign	-0.68
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.25	T;T;T
MetaRNN	Benign	0.000078	T;T;T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	1.7	L;.;.
MutationTaster	Benign	1.0	P;P;P;P
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.39	N;N;N
REVEL	Benign	0.021
Sift	Benign	0.055	T;D;D
Sift4G	Benign	0.17	T;T;T
Polyphen		0.67	P;.;P
Vest4		0.086
MPC		0.064
ClinPred		0.0078	T
GERP RS		1.7
Varity_R		0.035
gMVP		0.041

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: rs7315731; hg19: chr12-46321514; COSMIC: COSV65478195; COSMIC: COSV65478195;