NM_014892.5:c.3232C>A

Variant names:

• chr6-154832811-C-A
• rs777031188
• NM_014892.5:c.3232C>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_014892.5(SCAF8):​c.3232C>A​(p.His1078Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000958 in 1,461,828 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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: 31)
  • Exomes 𝑓: 0.0000096 (0 hom.)
• Consequence: SCAF8 NM_014892.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.46

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04281071).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCAF8	NM_014892.5	c.3232C>A	p.His1078Asn	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.3232C>A	p.His1078Asn	missense_variant	Exon 20 of 20	2	NM_014892.5	ENSP00000356146.3
SCAF8	ENST00000417268.3	c.3466C>A	p.His1156Asn	missense_variant	Exon 21 of 21	2		ENSP00000413098.2
SCAF8	ENST00000367186.7	c.3430C>A	p.His1144Asn	missense_variant	Exon 22 of 22	2		ENSP00000356154.4
TIAM2	ENST00000461783	c.-1159C>A		5_prime_UTR_variant	Exon 1 of 29	2		ENSP00000437188.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD3 exomes AF: 0.00000399 AC: 1 AN: 250514 Hom.: 0 AF XY: 0.00000738 AC XY: 1 AN XY: 135458

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000884

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000958 AC: 14 AN: 1461828 Hom.: 0 Cov.: 33 AF XY: 0.0000124 AC XY: 9 AN XY: 727210

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: 0.0000126

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ExAC AF: 0.00000824 AC: 1

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.048
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	19
DANN	Benign	0.90
DEOGEN2	Benign	0.011	T;.;T
Eigen	Benign	-0.33
Eigen_PC	Benign	-0.049
FATHMM_MKL	Benign	0.71	D
LIST_S2	Benign	0.78	T;T;T
M_CAP	Benign	0.0016	T
MetaRNN	Benign	0.043	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-1.6	N;.;.
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	0.36	N;N;.
REVEL	Benign	0.030
Sift	Benign	0.46	T;T;.
Sift4G	Benign	0.60	T;T;T
Polyphen		0.0090	B;.;.
Vest4		0.066
MutPred		0.19		.;Gain of relative solvent accessibility (P = 0.0289);.;
MVP		0.15
MPC		0.055
ClinPred		0.10	T
GERP RS		4.8
Varity_R		0.062
gMVP		0.088

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

LitVar

Other links and lift over

dbSNP: rs777031188; hg19: chr6-155153945;