19-49651236-G-T

Position:

• chr19-49651236-G-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_021228.3(SCAF1):​c.847G>T​(p.Asp283Tyr) 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. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 27)
• Consequence: SCAF1 NM_021228.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.29

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.054103076).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCAF1	NM_021228.3	c.847G>T	p.Asp283Tyr	missense_variant	7/11	ENST00000360565.8	NP_067051.2
SCAF1	XM_011527194.4	c.856G>T	p.Asp286Tyr	missense_variant	7/11		XP_011525496.1
SCAF1	XM_005259122.6	c.847G>T	p.Asp283Tyr	missense_variant	7/11		XP_005259179.1
SCAF1	XM_017027083.3	c.577G>T	p.Asp193Tyr	missense_variant	4/8		XP_016882572.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCAF1	ENST00000360565.8	c.847G>T	p.Asp283Tyr	missense_variant	7/11	2	NM_021228.3	ENSP00000353769.2

Frequencies

GnomAD3 genomes Cov.: 27

GnomAD4 exome Cov.: 37

GnomAD4 genome Cov.: 27

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 19, 2022

The c.847G>T (p.D283Y) alteration is located in exon 7 (coding exon 6) of the SCAF1 gene. This alteration results from a G to T substitution at nucleotide position 847, causing the aspartic acid (D) at amino acid position 283 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	19
DANN	Benign	0.34
DEOGEN2	Benign	0.042	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.32	T
M_CAP	Uncertain	0.12	D
MetaRNN	Benign	0.054	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	-0.82	N
REVEL	Benign	0.070
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.036	D
Polyphen		0.0	B
Vest4		0.25
MutPred		0.097		Gain of phosphorylation at D283 (P = 0.0101);
MVP		0.043
MPC		0.78
ClinPred		0.13	T
GERP RS		1.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.8
Varity_R		0.099
gMVP		0.27

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-50154493;