chr11-32613505-T-C

Variant names:

• chr11-32613505-T-C
• rs769157609
• NM_001008391.4:c.2813A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001008391.4(CCDC73):​c.2813A>G​(p.Asp938Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,824 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D938V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CCDC73 NM_001008391.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.803
• Publications: 0 publications found

Genes affected

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

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.029904813).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC73	NM_001008391.4	c.2813A>G	p.Asp938Gly	missense_variant	Exon 16 of 18	ENST00000335185.10	NP_001008392.2
CCDC73	XM_047427029.1	c.2813A>G	p.Asp938Gly	missense_variant	Exon 21 of 23		XP_047282985.1
CCDC73	XM_047427030.1	c.2813A>G	p.Asp938Gly	missense_variant	Exon 16 of 18		XP_047282986.1
CCDC73	XM_047427031.1	c.2555A>G	p.Asp852Gly	missense_variant	Exon 15 of 17		XP_047282987.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC73	ENST00000335185.10	c.2813A>G	p.Asp938Gly	missense_variant	Exon 16 of 18	2	NM_001008391.4	ENSP00000335325.5
CCDC73	ENST00000528333.1	c.136-10485A>G		intron_variant	Intron 1 of 1	3		ENSP00000434365.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461824 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727214

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39686

South Asian (SAS) AF: 0.00 AC: 0 AN: 86250

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111974

Other (OTH) AF: 0.00 AC: 0 AN: 60392

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.068
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	7.1
DANN	Benign	0.091
DEOGEN2	Benign	0.0044	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.0044	N
LIST_S2	Benign	0.52	T
M_CAP	Benign	0.0024	T
MetaRNN	Benign	0.030	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	-1.8	N
PhyloP100		0.80
PrimateAI	Benign	0.22	T
PROVEAN	Benign	0.67	N
REVEL	Benign	0.043
Sift	Benign	1.0	T
Sift4G	Benign	0.81	T
Polyphen		0.0	B
Vest4		0.090
MutPred		0.26		Loss of ubiquitination at K943 (P = 0.0326);
MVP		0.076
MPC		0.15
ClinPred		0.020	T
GERP RS		0.95
Varity_R		0.028
gMVP		0.097
Mutation Taster		=95/5	polymorphism

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

Other links and lift over

dbSNP: rs769157609; hg19: chr11-32635051;