rs149853604

Variant names:

• chr11-32613532-G-A
• rs149853604
• NM_001008391.4:c.2786C>T

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.2786C>T​(p.Ser929Phe) variant causes a missense change. The variant allele was found at a frequency of 0.00306 in 1,614,104 control chromosomes in the GnomAD database, including 15 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0025 (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: 4.89
• Publications: 5 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=0.0036777854).
• BP6: Variant 11-32613532-G-A is Benign according to our data. Variant chr11-32613532-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2641707.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.2786C>T	p.Ser929Phe	missense_variant	Exon 16 of 18	ENST00000335185.10	NP_001008392.2
CCDC73	XM_047427029.1	c.2786C>T	p.Ser929Phe	missense_variant	Exon 21 of 23		XP_047282985.1
CCDC73	XM_047427030.1	c.2786C>T	p.Ser929Phe	missense_variant	Exon 16 of 18		XP_047282986.1
CCDC73	XM_047427031.1	c.2528C>T	p.Ser843Phe	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.2786C>T	p.Ser929Phe	missense_variant	Exon 16 of 18	2	NM_001008391.4	ENSP00000335325.5
CCDC73	ENST00000528333.1	c.136-10512C>T		intron_variant	Intron 1 of 1	3		ENSP00000434365.1

Frequencies

GnomAD3 genomes AF: 0.00255 AC: 388 AN: 152146 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: 0.000283

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00326

Gnomad OTH AF: 0.00526

GnomAD2 exomes AF: 0.00259 AC: 645 AN: 249498 AF XY: 0.00296

Gnomad AFR exome AF: 0.000581

Gnomad AMR exome AF: 0.00191

Gnomad ASJ exome AF: 0.0000993

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000371

Gnomad NFE exome AF: 0.00282

Gnomad OTH exome AF: 0.00363

GnomAD4 exome AF: 0.00311 AC: 4550 AN: 1461840 Hom.: 14 Cov.: 33 AF XY: 0.00329 AC XY: 2390 AN XY: 727224

African (AFR) AF: 0.000568 AC: 19 AN: 33480

American (AMR) AF: 0.00203 AC: 91 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.000115 AC: 3 AN: 26130

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

South Asian (SAS) AF: 0.00722 AC: 623 AN: 86254

European-Finnish (FIN) AF: 0.000206 AC: 11 AN: 53420

Middle Eastern (MID) AF: 0.00780 AC: 45 AN: 5768

European-Non Finnish (NFE) AF: 0.00322 AC: 3579 AN: 1111986

Other (OTH) AF: 0.00296 AC: 179 AN: 60392

GnomAD4 genome AF: 0.00255 AC: 388 AN: 152264 Hom.: 1 Cov.: 32 AF XY: 0.00239 AC XY: 178 AN XY: 74440

African (AFR) AF: 0.000770 AC: 32 AN: 41560

American (AMR) AF: 0.00504 AC: 77 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00850 AC: 41 AN: 4824

European-Finnish (FIN) AF: 0.000283 AC: 3 AN: 10606

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

European-Non Finnish (NFE) AF: 0.00326 AC: 222 AN: 68010

Other (OTH) AF: 0.00521 AC: 11 AN: 2112

Alfa AF: 0.00275 Hom.: 4

Bravo AF: 0.00268

TwinsUK AF: 0.00431 AC: 16

ALSPAC AF: 0.00311 AC: 12

ESP6500AA AF: 0.000817 AC: 3

ESP6500EA AF: 0.00318 AC: 26

ExAC AF: 0.00269 AC: 325

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	0.15
BayesDel_addAF	Benign	-0.46	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.049	T
Eigen	Benign	-0.29
Eigen_PC	Benign	-0.22
FATHMM_MKL	Benign	0.60	D
LIST_S2	Benign	0.68	T
MetaRNN	Benign	0.0037	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.69	N
PhyloP100		4.9
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.095
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.0050	D
Polyphen		0.53	P
Vest4		0.27
MVP		0.055
MPC		0.22
ClinPred		0.023	T
GERP RS		4.2
Varity_R		0.11
gMVP		0.12
Mutation Taster		=96/4	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: rs149853604; hg19: chr11-32635078;