rs965442864

Variant names:

• chr6-154733494-C-A
• NM_014892.5:c.-407C>A

Your query was ambiguous. Multiple possible variants found:

• chr6-154733494-C-A
• chr6-154733494-C-T

Variant summary

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

The NM_001286188.1(SCAF8):​c.72C>A​(p.Ser24Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000855 in 1,170,160 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 10/15 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 8.5e-7 (0 hom.)
• Consequence: SCAF8 NM_001286188.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.368

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15993607).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCAF8	NM_014892.5	c.-407C>A		5_prime_UTR_variant	Exon 1 of 20	ENST00000367178.8	NP_055707.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCAF8	ENST00000367178	c.-407C>A		5_prime_UTR_variant	Exon 1 of 20	2	NM_014892.5	ENSP00000356146.3
SCAF8	ENST00000417268.3	c.72C>A	p.Ser24Arg	missense_variant	Exon 1 of 21	2		ENSP00000413098.2
SCAF8	ENST00000367186.7	c.72C>A	p.Ser24Arg	missense_variant	Exon 1 of 22	2		ENSP00000356154.4
SCAF8	ENST00000461219.5	n.117C>A		non_coding_transcript_exon_variant	Exon 1 of 6	5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 8.55e-7 AC: 1 AN: 1170160 Hom.: 0 Cov.: 30 AF XY: 0.00000176 AC XY: 1 AN XY: 567198

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000103

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.069	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0073	.;T
Eigen	Benign	-0.35
Eigen_PC	Benign	-0.33
FATHMM_MKL	Benign	0.17	N
LIST_S2	Benign	0.36	T;T
M_CAP	Pathogenic	0.56	D
MetaRNN	Benign	0.16	T;T
MetaSVM	Benign	-1.1	T
PROVEAN	Benign	-0.10	N;.
REVEL	Benign	0.056
Sift	Benign	0.030	D;.
Sift4G	Benign	0.45	T;T
Vest4		0.19
MutPred		0.14		Loss of phosphorylation at S24 (P = 0.0062);Loss of phosphorylation at S24 (P = 0.0062);
MVP		0.36
ClinPred		0.75	D
GERP RS		1.5
RBP_binding_hub_radar		1.0
RBP_regulation_power_radar		4.2
gMVP		0.11

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: chr6-155054628;