Genetic Variant NM_014892.5:c.3232C>T (chr6-154832811-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_014892.5(SCAF8):c.3232C>T(p.His1078Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000658 in 152,060 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 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: 𝑓 0.0000066 ( 0 hom., cov: 31)

Consequence

SCAF8
NM_014892.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.46

Variant links:

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]

SCAF8 links:

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]

TIAM2 links:

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ACMG classification

Classification made for transcript

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=0.12837684).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCAF8	NM_014892.5 link	c.3232C>T	p.His1078Tyr	missense_variant	Exon 20 of 20	ENST00000367178.8	NP_055707.3	Q9UPN6-1B7Z3A4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SCAF8	ENST00000367178.8 link	c.3232C>T	p.His1078Tyr	missense_variant	Exon 20 of 20	2	NM_014892.5	ENSP00000356146.3	Q9UPN6-1
SCAF8	ENST00000417268.3 link	c.3466C>T	p.His1156Tyr	missense_variant	Exon 21 of 21	2		ENSP00000413098.2	A0A0A0MT33
SCAF8	ENST00000367186.7 link	c.3430C>T	p.His1144Tyr	missense_variant	Exon 22 of 22	2		ENSP00000356154.4	Q9UPN6-2
TIAM2	ENST00000461783 link	c.-1159C>T		5_prime_UTR_variant	Exon 1 of 29	2		ENSP00000437188.2	Q8IVF5-1

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

151942

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000658

AC:

AN:

152060

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74312

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.092

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.48

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.021

T;.;T

Eigen

Benign

0.15

Eigen_PC

Uncertain

0.30

FATHMM_MKL

Uncertain

0.84

LIST_S2

Uncertain

0.91

D;D;D

M_CAP

Benign

0.0045

MetaRNN

Benign

0.13

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

N;.;.

PrimateAI

Uncertain

0.55

PROVEAN

Benign

-0.78

N;N;.

REVEL

Benign

0.068

Sift

Uncertain

0.010

D;D;.

Sift4G

Benign

0.067

T;T;T

Polyphen

0.97

D;.;.

Vest4

0.15

MutPred

0.26

.;Gain of phosphorylation at H1144 (P = 0.0545);.;

MVP

0.19

MPC

0.21

ClinPred

0.41

GERP RS

4.8

Varity_R

0.093

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over