6-154810143-C-A

Variant names:

• chr6-154810143-C-A
• NM_014892.5:c.1355C>A

Variant summary

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

The NM_014892.5(SCAF8):​c.1355C>A​(p.Ala452Asp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SCAF8 NM_014892.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.71

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCAF8	NM_014892.5	c.1355C>A	p.Ala452Asp	missense_variant	Exon 12 of 20	ENST00000367178.8	NP_055707.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCAF8	ENST00000367178.8	c.1355C>A	p.Ala452Asp	missense_variant	Exon 12 of 20	2	NM_014892.5	ENSP00000356146.3
SCAF8	ENST00000417268.3	c.1589C>A	p.Ala530Asp	missense_variant	Exon 13 of 21	2		ENSP00000413098.2
SCAF8	ENST00000367186.7	c.1553C>A	p.Ala518Asp	missense_variant	Exon 14 of 22	2		ENSP00000356154.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 05, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1355C>A (p.A452D) alteration is located in exon 12 (coding exon 12) of the SCAF8 gene. This alteration results from a C to A substitution at nucleotide position 1355, causing the alanine (A) at amino acid position 452 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	Pathogenic	0.93
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Uncertain	0.030
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.018	T;.;T
Eigen	Uncertain	0.57
Eigen_PC	Uncertain	0.64
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.84	T;T;T
M_CAP	Benign	0.017	T
MetaRNN	Uncertain	0.52	D;D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-1.9	N;.;.
PrimateAI	Pathogenic	0.87	D
PROVEAN	Benign	0.49	N;N;.
REVEL	Uncertain	0.32
Sift	Uncertain	0.015	D;D;.
Sift4G	Benign	0.52	T;T;T
Polyphen		1.0	D;.;.
Vest4		0.69
MutPred		0.37		.;Gain of relative solvent accessibility (P = 0.0215);.;
MVP		0.31
MPC		1.0
ClinPred		0.94	D
GERP RS		5.9
Varity_R		0.15
gMVP		0.70

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: chr6-155131277;