chr11-32613442-A-C

Variant names:

• chr11-32613442-A-C
• rs117521878
• NM_001008391.4:c.2876T>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001008391.4(CCDC73):​c.2876T>G​(p.Val959Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00305 in 1,611,548 control chromosomes in the GnomAD database, including 15 homozygotes. 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 Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0026 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0031 (14 hom.)
• Consequence: CCDC73 NM_001008391.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.22
• Publications: 1 publications found

Genes affected

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

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0032474399).
• BP6: Variant 11-32613442-A-C is Benign according to our data. Variant chr11-32613442-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 2641706.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome4 at 14 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC73	NM_001008391.4	c.2876T>G	p.Val959Gly	missense_variant	Exon 16 of 18	ENST00000335185.10	NP_001008392.2
CCDC73	XM_047427029.1	c.2876T>G	p.Val959Gly	missense_variant	Exon 21 of 23		XP_047282985.1
CCDC73	XM_047427030.1	c.2876T>G	p.Val959Gly	missense_variant	Exon 16 of 18		XP_047282986.1
CCDC73	XM_047427031.1	c.2618T>G	p.Val873Gly	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.2876T>G	p.Val959Gly	missense_variant	Exon 16 of 18	2	NM_001008391.4	ENSP00000335325.5
CCDC73	ENST00000528333.1	c.136-10422T>G		intron_variant	Intron 1 of 1	3		ENSP00000434365.1

Frequencies

GnomAD3 genomes AF: 0.00256 AC: 390 AN: 152210 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000772

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00504

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00849

Gnomad FIN AF: 0.000376

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00328

Gnomad OTH AF: 0.00526

GnomAD2 exomes AF: 0.00260 AC: 647 AN: 248466 AF XY: 0.00299

Gnomad AFR exome AF: 0.000581

Gnomad AMR exome AF: 0.00193

Gnomad ASJ exome AF: 0.000100

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000465

Gnomad NFE exome AF: 0.00283

Gnomad OTH exome AF: 0.00365

GnomAD4 exome AF: 0.00310 AC: 4530 AN: 1459220 Hom.: 14 Cov.: 32 AF XY: 0.00328 AC XY: 2377 AN XY: 725496

African (AFR) AF: 0.000569 AC: 19 AN: 33414

American (AMR) AF: 0.00205 AC: 91 AN: 44452

Ashkenazi Jewish (ASJ) AF: 0.000115 AC: 3 AN: 26052

East Asian (EAS) AF: 0.00 AC: 0 AN: 39648

South Asian (SAS) AF: 0.00720 AC: 619 AN: 85930

European-Finnish (FIN) AF: 0.000300 AC: 16 AN: 53388

Middle Eastern (MID) AF: 0.00765 AC: 44 AN: 5754

European-Non Finnish (NFE) AF: 0.00320 AC: 3558 AN: 1110282

Other (OTH) AF: 0.00299 AC: 180 AN: 60300

GnomAD4 genome AF: 0.00256 AC: 390 AN: 152328 Hom.: 1 Cov.: 32 AF XY: 0.00240 AC XY: 179 AN XY: 74494

African (AFR) AF: 0.000770 AC: 32 AN: 41572

American (AMR) AF: 0.00503 AC: 77 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5196

South Asian (SAS) AF: 0.00850 AC: 41 AN: 4826

European-Finnish (FIN) AF: 0.000376 AC: 4 AN: 10628

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.00328 AC: 223 AN: 68020

Other (OTH) AF: 0.00520 AC: 11 AN: 2114

Alfa AF: 0.00191 Hom.: 2

Bravo AF: 0.00269

TwinsUK AF: 0.00431 AC: 16

ALSPAC AF: 0.00311 AC: 12

ESP6500AA AF: 0.000825 AC: 3

ESP6500EA AF: 0.00319 AC: 26

ExAC AF: 0.00270 AC: 326

Asia WGS AF: 0.00318 AC: 11 AN: 3478

EpiCase AF: 0.00333

EpiControl AF: 0.00373

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jan 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

CCDC73: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.094
BayesDel_addAF	Benign	-0.58	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	0.031
DANN	Benign	0.60
DEOGEN2	Benign	0.0071	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.050	N
LIST_S2	Benign	0.16	T
MetaRNN	Benign	0.0032	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.49	N
PhyloP100		-1.2
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-0.90	N
REVEL	Benign	0.030
Sift	Benign	0.16	T
Sift4G	Benign	0.086	T
Polyphen		0.0010	B
Vest4		0.11
MVP		0.17
MPC		0.15
ClinPred		0.0059	T
GERP RS		-11
Varity_R		0.054
gMVP		0.087
Mutation Taster		=97/3	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: rs117521878; hg19: chr11-32634988;