19-49646556-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_021228.3(SCAF1):c.292G>T(p.Ala98Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0139 in 1,613,980 control chromosomes in the GnomAD database, including 227 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0084 (11 hom., cov: 32)
  • Exomes 𝑓: 0.015 (216 hom.)
• Consequence: SCAF1 NM_021228.3 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0190

Genes affected

SCAF1 (HGNC:30403): (SR-related CTD associated factor 1) Enables RNA polymerase II C-terminal domain binding activity. Predicted to be involved in RNA splicing; mRNA processing; and transcription by RNA polymerase II. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0058086216).
• BP6: Variant 19-49646556-G-T is Benign according to our data. Variant chr19-49646556-G-T is described in ClinVar as [Benign]. Clinvar id is 710946.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4_exome allele frequency = 0.0145 (21232/1461724) while in subpopulation NFE AF= 0.0177 (19687/1111942). AF 95% confidence interval is 0.0175. There are 216 homozygotes in gnomad4_exome. There are 10118 alleles in male gnomad4_exome subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 10 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SCAF1	NM_021228.3	c.292G>T	p.Ala98Ser	missense_variant	5/11	ENST00000360565.8
SCAF1	XM_011527194.4	c.301G>T	p.Ala101Ser	missense_variant	5/11
SCAF1	XM_005259122.6	c.292G>T	p.Ala98Ser	missense_variant	5/11
SCAF1	XM_017027083.3	c.22G>T	p.Ala8Ser	missense_variant	2/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SCAF1	ENST00000360565.8	c.292G>T	p.Ala98Ser	missense_variant	5/11	2	NM_021228.3	P1
SCAF1	ENST00000598359.5	c.292G>T	p.Ala98Ser	missense_variant	5/7	3
SCAF1	ENST00000595242.3	c.296G>T	p.Arg99Leu	missense_variant	4/4	3
SCAF1	ENST00000601038.5	c.292G>T	p.Ala98Ser	missense_variant	4/4	3

Frequencies

GnomAD3 genomes AF: 0.00842 AC: 1281 AN: 152138 Hom.: 10 Cov.: 32

Gnomad AFR AF: 0.00282

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00687

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000827

Gnomad FIN AF: 0.00528

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0145

Gnomad OTH AF: 0.00623

GnomAD3 exomes AF: 0.00678 AC: 1701 AN: 250900 Hom.: 17 AF XY: 0.00677 AC XY: 919 AN XY: 135770

Gnomad AFR exome AF: 0.00223

Gnomad AMR exome AF: 0.00289

Gnomad ASJ exome AF: 0.000298

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000131

Gnomad FIN exome AF: 0.00504

Gnomad NFE exome AF: 0.0124

Gnomad OTH exome AF: 0.00751

GnomAD4 exome AF: 0.0145 AC: 21232 AN: 1461724 Hom.: 216 Cov.: 32 AF XY: 0.0139 AC XY: 10118 AN XY: 727182

Gnomad4 AFR exome AF: 0.00242

Gnomad4 AMR exome AF: 0.00326

Gnomad4 ASJ exome AF: 0.000191

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000220

Gnomad4 FIN exome AF: 0.00544

Gnomad4 NFE exome AF: 0.0177

Gnomad4 OTH exome AF: 0.0166

GnomAD4 genome AF: 0.00843 AC: 1283 AN: 152256 Hom.: 11 Cov.: 32 AF XY: 0.00758 AC XY: 564 AN XY: 74450

Gnomad4 AFR AF: 0.00282

Gnomad4 AMR AF: 0.00686

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00124

Gnomad4 FIN AF: 0.00528

Gnomad4 NFE AF: 0.0145

Gnomad4 OTH AF: 0.00616

Alfa AF: 0.0114 Hom.: 28

Bravo AF: 0.00902

TwinsUK AF: 0.0148 AC: 55

ALSPAC AF: 0.0184 AC: 71

ESP6500AA AF: 0.00340 AC: 15

ESP6500EA AF: 0.0136 AC: 117

ExAC AF: 0.00670 AC: 813

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.0137

EpiControl AF: 0.0121

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jun 26, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.078
BayesDel_addAF	Benign	-0.64	T
BayesDel_noAF	Benign	-0.67
Cadd	Benign	4.4
Dann	Benign	0.60
DEOGEN2	Benign	0.033	T;T;T
Eigen	Benign	-0.96
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.064	N
LIST_S2	Benign	0.48	T;T;T
MetaRNN	Benign	0.0033	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.55	N;.;.
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.52	N;.;.
REVEL	Benign	0.028
Sift	Benign	0.032	D;.;.
Sift4G	Benign	0.14	T;D;D
Polyphen		0.51	P;.;.
Vest4		0.14
MVP		0.093
MPC		0.58
ClinPred		0.0096	T
GERP RS		1.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.027
gMVP		0.088

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: rs45513592; hg19: chr19-50149813;