chr11-32611171-C-A

Variant names:

• chr11-32611171-C-A
• rs780962499
• NM_001008391.4:c.2991G>T

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.2991G>T​(p.Met997Ile) 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. 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CCDC73 NM_001008391.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.24
• 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=0.025938272).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC73	NM_001008391.4	c.2991G>T	p.Met997Ile	missense_variant	Exon 17 of 18	ENST00000335185.10	NP_001008392.2
CCDC73	XM_047427029.1	c.2991G>T	p.Met997Ile	missense_variant	Exon 22 of 23		XP_047282985.1
CCDC73	XM_047427030.1	c.2991G>T	p.Met997Ile	missense_variant	Exon 17 of 18		XP_047282986.1
CCDC73	XM_047427031.1	c.2733G>T	p.Met911Ile	missense_variant	Exon 16 of 17		XP_047282987.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC73	ENST00000335185.10	c.2991G>T	p.Met997Ile	missense_variant	Exon 17 of 18	2	NM_001008391.4	ENSP00000335325.5
CCDC73	ENST00000528333.1	c.136-8151G>T		intron_variant	Intron 1 of 1	3		ENSP00000434365.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	8.6
DANN	Benign	0.73
DEOGEN2	Benign	0.0047	T
Eigen	Benign	-0.96
Eigen_PC	Benign	-0.69
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.18	T
M_CAP	Benign	0.0013	T
MetaRNN	Benign	0.026	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-1.1	N
PhyloP100		1.2
PrimateAI	Benign	0.25	T
PROVEAN	Benign	0.74	N
REVEL	Benign	0.091
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.22
MutPred		0.11		Gain of methylation at K999 (P = 0.0981);
MVP		0.13
MPC		0.12
ClinPred		0.048	T
GERP RS		4.4
Varity_R		0.055
gMVP		0.062
Mutation Taster		=98/2	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: rs780962499; hg19: chr11-32632717;