NM_014892.5:c.3200_3204delTAAGA

Variant names:

• chr6-154832777-TATAAG-T
• NM_014892.5:c.3200_3204delTAAGA

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 6P and 2B. PVS1_Strong PM2 BP6_Moderate

The NM_014892.5(SCAF8):​c.3200_3204delTAAGA​(p.Ile1067ArgfsTer20) variant causes a frameshift change. The variant allele was found at a frequency of 0.000000684 in 1,461,844 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SCAF8 NM_014892.5 frameshift
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 6.97
• 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 4 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.161 CDS is truncated, and there are 0 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 6-154832777-TATAAG-T is Benign according to our data. Variant chr6-154832777-TATAAG-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2429804.Status of the report is criteria_provided_single_submitter, 1 stars.

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.3200_3204delTAAGA	p.Ile1067ArgfsTer20	frameshift	Exon 20 of 20	NP_055707.3
	SCAF8	NM_001286188.1		c.3434_3438delTAAGA	p.Ile1145ArgfsTer20	frameshift	Exon 21 of 21	NP_001273117.1	Q9UPN6
	SCAF8	NM_001286189.1		c.3398_3402delTAAGA	p.Ile1133ArgfsTer20	frameshift	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.3200_3204delTAAGA	p.Ile1067ArgfsTer20	frameshift	Exon 20 of 20	ENSP00000356146.3	Q9UPN6-1
	SCAF8	ENST00000417268.3	TSL:2	c.3434_3438delTAAGA	p.Ile1145ArgfsTer20	frameshift	Exon 21 of 21	ENSP00000413098.2	A0A0A0MT33
	SCAF8	ENST00000367186.7	TSL:2	c.3398_3402delTAAGA	p.Ile1133ArgfsTer20	frameshift	Exon 22 of 22	ENSP00000356154.4	Q9UPN6-2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461844 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 727222

African (AFR) AF: 0.00 AC: 0 AN: 33480

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

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39690

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53404

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

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111994

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 31

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Autism spectrum disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		7.0

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

hg19: chr6-155153911;