17-63589038-A-G

Position:

• chr17-63589038-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_005828.5(DCAF7):​c.895A>G​(p.Met299Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 11/19 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: 32)
• Consequence: DCAF7 NM_005828.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.11

Genes affected

DCAF7 (HGNC:30915): (DDB1 and CUL4 associated factor 7) This gene encodes a protein with multiple WD40 repeats which facilitate protein-protein interactions and thereby enable the assembly of multiprotein complexes. This protein has been shown to function as a scaffold protein for protein complexes involved in kinase signaling. This highly conserved gene is present in eukaryotic plants, fungi, and animals. The ortholog of this gene was first identified in plants as a key regulator of anthocyanin biosynthesis and flower pigmentation. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2014]

ENSG00000288894 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.36029953).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DCAF7	NM_005828.5	c.895A>G	p.Met299Val	missense_variant	7/7	ENST00000614556.5	NP_005819.3
DCAF7	NR_073585.2	n.1096A>G		non_coding_transcript_exon_variant	7/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DCAF7	ENST00000614556.5	c.895A>G	p.Met299Val	missense_variant	7/7	1	NM_005828.5	ENSP00000483236.1
ENSG00000288894	ENST00000690765.1	n.895A>G		non_coding_transcript_exon_variant	7/12			ENSP00000510085.1

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

Aug 04, 2024

The c.895A>G (p.M299V) alteration is located in exon 7 (coding exon 7) of the DCAF7 gene. This alteration results from a A to G substitution at nucleotide position 895, causing the methionine (M) at amino acid position 299 to be replaced by a valine (V). 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	Pathogenic	0.70
BayesDel_addAF	Benign	0.011	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	22
DANN	Benign	0.93
DEOGEN2	Benign	0.037	T;.
Eigen	Benign	0.050
Eigen_PC	Benign	0.22
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.94	.;D
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.36	T;T
MetaSVM	Benign	-1.0	T
PrimateAI	Pathogenic	0.88	D
PROVEAN	Benign	-2.2	.;N
REVEL	Benign	0.22
Sift	Benign	0.51	.;T
Sift4G	Benign	0.51	T;T
Polyphen		0.0040	B;.
Vest4		0.61
MutPred		0.49		Loss of catalytic residue at M299 (P = 0.0367);.;
MVP		0.59
MPC		1.7
ClinPred		0.94	D
GERP RS		5.0
Varity_R		0.26
gMVP		0.66

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: chr17-61666400;