6-154805444-A-T

Position:

• chr6-154805444-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_014892.5(SCAF8):​c.939A>T​(p.Glu313Asp) 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. 12/21 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: SCAF8 NM_014892.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.242

Genes affected

SCAF8 (HGNC:20959): (SR-related CTD associated factor 8) Enables RNA binding activity and RNA polymerase II C-terminal domain phosphoserine binding activity. Involved in negative regulation of termination of RNA polymerase II transcription, poly(A)-coupled and positive regulation of DNA-templated transcription, elongation. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2881471).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCAF8	NM_014892.5	c.939A>T	p.Glu313Asp	missense_variant	9/20	ENST00000367178.8	NP_055707.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCAF8	ENST00000367178.8	c.939A>T	p.Glu313Asp	missense_variant	9/20	2	NM_014892.5	ENSP00000356146	P1
SCAF8	ENST00000417268.3	c.1173A>T	p.Glu391Asp	missense_variant	10/21	2		ENSP00000413098
SCAF8	ENST00000367186.7	c.1137A>T	p.Glu379Asp	missense_variant	11/22	2		ENSP00000356154

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

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 20, 2023

The c.939A>T (p.E313D) alteration is located in exon 9 (coding exon 9) of the SCAF8 gene. This alteration results from a A to T substitution at nucleotide position 939, causing the glutamic acid (E) at amino acid position 313 to be replaced by an aspartic acid (D). 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	0.28
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	19
DANN	Uncertain	0.98
DEOGEN2	Benign	0.023	T;.;T
Eigen	Benign	-0.11
Eigen_PC	Benign	-0.23
FATHMM_MKL	Benign	0.65	D
LIST_S2	Uncertain	0.93	D;D;D
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.29	T;T;T
MetaSVM	Benign	-1.2	T
MutationAssessor	Uncertain	2.1	M;.;.
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-0.44	N;N;.
REVEL	Benign	0.18
Sift	Uncertain	0.0050	D;D;.
Sift4G	Benign	0.51	T;T;T
Polyphen		0.99	D;.;.
Vest4		0.64
MutPred		0.15		.;Loss of helix (P = 0.0444);.;
MVP		0.14
MPC		0.64
ClinPred		0.70	D
GERP RS		-5.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.30
gMVP		0.16

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: chr6-155126578;