chr11-32613444-A-T

Position:

• chr11-32613444-A-T

Variant summary

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

The NM_001008391.4(CCDC73):​c.2874T>A​(p.Asp958Glu) 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: CCDC73 NM_001008391.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0920

Genes affected

CCDC73 (HGNC:23261): (coiled-coil domain containing 73)

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=0.04159251).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC73	NM_001008391.4	c.2874T>A	p.Asp958Glu	missense_variant	16/18	ENST00000335185.10	NP_001008392.2
CCDC73	XM_047427029.1	c.2874T>A	p.Asp958Glu	missense_variant	21/23		XP_047282985.1
CCDC73	XM_047427030.1	c.2874T>A	p.Asp958Glu	missense_variant	16/18		XP_047282986.1
CCDC73	XM_047427031.1	c.2616T>A	p.Asp872Glu	missense_variant	15/17		XP_047282987.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC73	ENST00000335185.10	c.2874T>A	p.Asp958Glu	missense_variant	16/18	2	NM_001008391.4	ENSP00000335325.5
CCDC73	ENST00000528333.1	c.136-10424T>A		intron_variant		3		ENSP00000434365.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

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

Oct 20, 2023

The c.2874T>A (p.D958E) alteration is located in exon 16 (coding exon 15) of the CCDC73 gene. This alteration results from a T to A substitution at nucleotide position 2874, causing the aspartic acid (D) at amino acid position 958 to be replaced by a glutamic acid (E). 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	0.13
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	0.010
DANN	Benign	0.20
DEOGEN2	Benign	0.0081	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.064	N
LIST_S2	Benign	0.31	T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.042	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.52	N
REVEL	Benign	0.0030
Sift	Benign	0.41	T
Sift4G	Benign	0.29	T
Polyphen		0.0020	B
Vest4		0.051
MutPred		0.26		Loss of sheet (P = 0.0817);
MVP		0.061
MPC		0.12
ClinPred		0.11	T
GERP RS		-1.8
Varity_R		0.025
gMVP		0.042

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: chr11-32634990;