chr6-154832716-G-C

Variant names:

• chr6-154832716-G-C
• rs1778783929
• NM_014892.5:c.3137G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014892.5(SCAF8):​c.3137G>C​(p.Arg1046Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,814 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: SCAF8 NM_014892.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.26
• Publications: 0 publications found

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]

TIAM2 (HGNC:11806): (TIAM Rac1 associated GEF 2) This gene encodes a guanine nucleotide exchange factor. A highly similar mouse protein specifically activates ras-related C3 botulinum substrate 1, converting this Rho-like guanosine triphosphatase (GTPase) from a guanosine diphosphate-bound inactive state to a guanosine triphosphate-bound active state. The encoded protein may play a role in neural cell development. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1768224).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014892.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCAF8	NM_014892.5	MANE Select	c.3137G>C	p.Arg1046Thr	missense	Exon 20 of 20	NP_055707.3
	SCAF8	NM_001286188.1		c.3371G>C	p.Arg1124Thr	missense	Exon 21 of 21	NP_001273117.1	Q9UPN6
	SCAF8	NM_001286189.1		c.3335G>C	p.Arg1112Thr	missense	Exon 22 of 22	NP_001273118.1	Q9UPN6-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCAF8	ENST00000367178.8	TSL:2 MANE Select	c.3137G>C	p.Arg1046Thr	missense	Exon 20 of 20	ENSP00000356146.3	Q9UPN6-1
	SCAF8	ENST00000417268.3	TSL:2	c.3371G>C	p.Arg1124Thr	missense	Exon 21 of 21	ENSP00000413098.2	A0A0A0MT33
	SCAF8	ENST00000367186.7	TSL:2	c.3335G>C	p.Arg1112Thr	missense	Exon 22 of 22	ENSP00000356154.4	Q9UPN6-2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1461814 Hom.: 0 Cov.: 33 AF XY: 0.00000275 AC XY: 2 AN XY: 727198

African (AFR) AF: 0.000119 AC: 4 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39688

South Asian (SAS) AF: 0.00 AC: 0 AN: 86246

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111974

Other (OTH) AF: 0.0000166 AC: 1 AN: 60392

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.71
BayesDel_addAF	Uncertain	0.022	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	23
DANN	Benign	0.97
DEOGEN2	Benign	0.041	T
Eigen	Uncertain	0.30
Eigen_PC	Uncertain	0.43
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-0.85	T
MutationAssessor	Benign	1.7	L
PhyloP100		8.3
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.13
Sift	Uncertain	0.0030	D
Sift4G	Benign	0.54	T
Polyphen		0.98	D
Vest4		0.37
MutPred		0.14		Gain of phosphorylation at R1112 (P = 0.0025)
MVP		0.25
MPC		0.39
ClinPred		0.85	D
GERP RS		5.6
PromoterAI		0.025	Neutral
Varity_R		0.17
gMVP		0.38
Mutation Taster		=91/9	polymorphism

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

Other links and lift over

dbSNP: rs1778783929; hg19: chr6-155153850;