6-154832716-G-A

Variant names:

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

Variant summary

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

The NM_014892.5(SCAF8):​c.3137G>A​(p.Arg1046Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,814 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SCAF8 NM_014892.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.26

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

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=0.18250751).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCAF8	NM_014892.5	c.3137G>A	p.Arg1046Lys	missense_variant	Exon 20 of 20	ENST00000367178.8	NP_055707.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCAF8	ENST00000367178.8	c.3137G>A	p.Arg1046Lys	missense_variant	Exon 20 of 20	2	NM_014892.5	ENSP00000356146.3
SCAF8	ENST00000417268.3	c.3371G>A	p.Arg1124Lys	missense_variant	Exon 21 of 21	2		ENSP00000413098.2
SCAF8	ENST00000367186.7	c.3335G>A	p.Arg1112Lys	missense_variant	Exon 22 of 22	2		ENSP00000356154.4
TIAM2	ENST00000461783	c.-1254G>A		5_prime_UTR_variant	Exon 1 of 29	2		ENSP00000437188.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461814 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 727198

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.033	T
BayesDel_noAF	Benign	-0.29
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.029	T;.;T
Eigen	Uncertain	0.43
Eigen_PC	Uncertain	0.52
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.86	D;D;D
M_CAP	Benign	0.0095	T
MetaRNN	Benign	0.18	T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.7	L;.;.
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-0.69	N;N;N
REVEL	Benign	0.063
Sift	Uncertain	0.011	D;D;D
Sift4G	Benign	0.87	T;T;T
Polyphen		0.96	P;.;.
Vest4		0.25
MutPred		0.16		.;Gain of ubiquitination at R1112 (P = 0.0016);.;
MVP		0.46
MPC		0.33
ClinPred		0.71	D
GERP RS		5.6
Varity_R		0.19
gMVP		0.30

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: chr6-155153850;