chr12-45927731-A-T

Variant names:

• chr12-45927731-A-T
• rs7315731
• NM_004719.3:c.1970T>A

Variant summary

Our verdict is Benign. The variant received -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. 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: 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
• Publications: 33 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004719.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCAF11	NM_004719.3	MANE Select	c.1970T>A	p.Phe657Tyr	missense	Exon 11 of 15	NP_004710.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCAF11	ENST00000369367.8	TSL:1 MANE Select	c.1970T>A	p.Phe657Tyr	missense	Exon 11 of 15	ENSP00000358374.3
	SCAF11	ENST00000549162.5	TSL:1	c.1394T>A	p.Phe465Tyr	missense	Exon 5 of 9	ENSP00000448864.1
	SCAF11	ENST00000465950.5	TSL:1	c.1025T>A	p.Phe342Tyr	missense	Exon 1 of 5	ENSP00000449812.1

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

GnomAD2 exomes AF: 0.463 AC: 115218 AN: 248810 AF XY: 0.474

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 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

African (AFR) AF: 0.146 AC: 4873 AN: 33324

American (AMR) AF: 0.409 AC: 18181 AN: 44496

Ashkenazi Jewish (ASJ) AF: 0.524 AC: 13666 AN: 26070

East Asian (EAS) AF: 0.477 AC: 18922 AN: 39662

South Asian (SAS) AF: 0.520 AC: 44621 AN: 85858

European-Finnish (FIN) AF: 0.499 AC: 26391 AN: 52846

Middle Eastern (MID) AF: 0.511 AC: 2939 AN: 5752

European-Non Finnish (NFE) AF: 0.492 AC: 546046 AN: 1109590

Other (OTH) AF: 0.472 AC: 28424 AN: 60248

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

African (AFR) AF: 0.154 AC: 6381 AN: 41474

American (AMR) AF: 0.397 AC: 6058 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.518 AC: 1796 AN: 3468

East Asian (EAS) AF: 0.546 AC: 2818 AN: 5164

South Asian (SAS) AF: 0.517 AC: 2490 AN: 4820

European-Finnish (FIN) AF: 0.521 AC: 5484 AN: 10532

Middle Eastern (MID) AF: 0.514 AC: 151 AN: 294

European-Non Finnish (NFE) AF: 0.489 AC: 33218 AN: 67952

Other (OTH) AF: 0.408 AC: 860 AN: 2108

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 v4.9

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
Eigen	Benign	-0.59
Eigen_PC	Benign	-0.68
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.25	T
MetaRNN	Benign	0.000078	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	1.7	L
PhyloP100		0.0060
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.39	N
REVEL	Benign	0.021
Sift	Benign	0.055	T
Sift4G	Benign	0.17	T
Polyphen		0.67	P
Vest4		0.086
MPC		0.064
ClinPred		0.0078	T
GERP RS		1.7
Varity_R		0.035
gMVP		0.041
Mutation Taster		=99/1	polymorphism (auto)

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