chr19-49646765-A-G

Position:

• chr19-49646765-A-G

Variant summary

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

The NM_021228.3(SCAF1):​c.413A>G​(p.Asp138Gly) 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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SCAF1 NM_021228.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.01

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 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=0.10235196).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SCAF1	NM_021228.3	c.413A>G	p.Asp138Gly	missense_variant	6/11	ENST00000360565.8
SCAF1	XM_011527194.4	c.422A>G	p.Asp141Gly	missense_variant	6/11
SCAF1	XM_005259122.6	c.413A>G	p.Asp138Gly	missense_variant	6/11
SCAF1	XM_017027083.3	c.143A>G	p.Asp48Gly	missense_variant	3/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SCAF1	ENST00000360565.8	c.413A>G	p.Asp138Gly	missense_variant	6/11	2	NM_021228.3	P1
SCAF1	ENST00000598359.5	c.413A>G	p.Asp138Gly	missense_variant	6/7	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

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

Oct 17, 2023

The c.413A>G (p.D138G) alteration is located in exon 6 (coding exon 5) of the SCAF1 gene. This alteration results from a A to G substitution at nucleotide position 413, causing the aspartic acid (D) at amino acid position 138 to be replaced by a glycine (G). 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	0.29
BayesDel_addAF	Benign	-0.093	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	20
DANN	Benign	0.96
DEOGEN2	Benign	0.044	T;T
Eigen	Benign	-0.41
Eigen_PC	Benign	-0.25
FATHMM_MKL	Benign	0.46	N
LIST_S2	Benign	0.56	T;T
M_CAP	Benign	0.028	D
MetaRNN	Benign	0.10	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.55	N;.
MutationTaster	Benign	0.95	N
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-1.4	N;.
REVEL	Benign	0.088
Sift	Pathogenic	0.0	D;.
Sift4G	Benign	0.20	T;T
Polyphen		0.0020	B;.
Vest4		0.17
MutPred		0.48		Loss of helix (P = 0.079);Loss of helix (P = 0.079);
MVP		0.068
MPC		0.83
ClinPred		0.49	T
GERP RS		2.3
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.0
Varity_R		0.15
gMVP		0.34

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: chr19-50150022;