chr11-65921337-A-C

Position:

• chr11-65921337-A-C

Variant summary

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

The NM_006442.4(DRAP1):​c.520A>C​(p.Thr174Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: DRAP1 NM_006442.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.864

Genes affected

DRAP1 (HGNC:3019): (DR1 associated protein 1) Transcriptional repression is a general mechanism for regulating transcriptional initiation in organisms ranging from yeast to humans. Accurate initiation of transcription from eukaryotic protein-encoding genes requires the assembly of a large multiprotein complex consisting of RNA polymerase II and general transcription factors such as TFIIA, TFIIB, and TFIID. DR1 is a repressor that interacts with the TATA-binding protein (TBP) of TFIID and prevents the formation of an active transcription complex by precluding the entry of TFIIA and/or TFIIB into the preinitiation complex. The protein encoded by this gene is a corepressor of transcription that interacts with DR1 to enhance DR1-mediated repression. The interaction between this corepressor and DR1 is required for corepressor function and appears to stabilize the TBP-DR1-DNA complex. [provided by RefSeq, Jul 2008]

DRAP1 (HGNC:):

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=0.05802113).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DRAP1	NM_006442.4	c.520A>C	p.Thr174Pro	missense_variant	7/7	ENST00000312515.7	NP_006433.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DRAP1	ENST00000312515.7	c.520A>C	p.Thr174Pro	missense_variant	7/7	1	NM_006442.4	ENSP00000307850.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 02, 2021

The c.520A>C (p.T174P) alteration is located in exon 7 (coding exon 7) of the DRAP1 gene. This alteration results from a A to C substitution at nucleotide position 520, causing the threonine (T) at amino acid position 174 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.056
BayesDel_addAF	Benign	-0.043	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	13
DANN	Benign	0.88
DEOGEN2	Benign	0.13	T;.;T;T;T
Eigen	Benign	-0.86
Eigen_PC	Benign	-0.83
FATHMM_MKL	Benign	0.39	N
LIST_S2	Benign	0.57	T;T;T;T;T
M_CAP	Benign	0.0042	T
MetaRNN	Benign	0.058	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.2	L;.;.;.;.
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-0.61	N;N;N;N;N
REVEL	Benign	0.078
Sift	Benign	0.20	T;T;T;T;T
Sift4G	Benign	0.22	T;T;T;T;T
Polyphen		0.023	B;.;.;.;.
Vest4		0.41
MutPred		0.13		Loss of phosphorylation at T174 (P = 0.0089);.;.;.;.;
MVP		0.16
MPC		0.14
ClinPred		0.10	T
GERP RS		0.99
Varity_R		0.059
gMVP		0.26

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: rs1854547882; hg19: chr11-65688808;