rs188950262

Variant names:

• chr11-32613550-C-A
• rs188950262
• NM_001008391.4:c.2768G>T

Your query was ambiguous. Multiple possible variants found:

• chr11-32613550-C-A
• chr11-32613550-C-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.2768G>T​(p.Ser923Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00678 in 1,614,104 control chromosomes in the GnomAD database, including 55 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S923R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0045 (6 hom., cov: 32)
  • Exomes 𝑓: 0.0070 (49 hom.)
• Consequence: CCDC73 NM_001008391.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.95
• Publications: 10 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=0.005057037).
• BP6: Variant 11-32613550-C-A is Benign according to our data. Variant chr11-32613550-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 2641708.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC73	NM_001008391.4	c.2768G>T	p.Ser923Ile	missense_variant	Exon 16 of 18	ENST00000335185.10	NP_001008392.2
CCDC73	XM_047427029.1	c.2768G>T	p.Ser923Ile	missense_variant	Exon 21 of 23		XP_047282985.1
CCDC73	XM_047427030.1	c.2768G>T	p.Ser923Ile	missense_variant	Exon 16 of 18		XP_047282986.1
CCDC73	XM_047427031.1	c.2510G>T	p.Ser837Ile	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.2768G>T	p.Ser923Ile	missense_variant	Exon 16 of 18	2	NM_001008391.4	ENSP00000335325.5
CCDC73	ENST00000528333.1	c.136-10530G>T		intron_variant	Intron 1 of 1	3		ENSP00000434365.1

Frequencies

GnomAD3 genomes AF: 0.00450 AC: 684 AN: 152142 Hom.: 6 Cov.: 32

Gnomad AFR AF: 0.00159

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00478

Gnomad ASJ AF: 0.00260

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00186

Gnomad FIN AF: 0.00160

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00739

Gnomad OTH AF: 0.00334

GnomAD2 exomes AF: 0.00487 AC: 1216 AN: 249518 AF XY: 0.00502

Gnomad AFR exome AF: 0.00232

Gnomad AMR exome AF: 0.00501

Gnomad ASJ exome AF: 0.00209

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00144

Gnomad NFE exome AF: 0.00746

Gnomad OTH exome AF: 0.00611

GnomAD4 exome AF: 0.00702 AC: 10258 AN: 1461844 Hom.: 49 Cov.: 33 AF XY: 0.00691 AC XY: 5028 AN XY: 727220

African (AFR) AF: 0.00143 AC: 48 AN: 33480

American (AMR) AF: 0.00505 AC: 226 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00230 AC: 60 AN: 26132

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

South Asian (SAS) AF: 0.00221 AC: 191 AN: 86256

European-Finnish (FIN) AF: 0.00161 AC: 86 AN: 53418

Middle Eastern (MID) AF: 0.000693 AC: 4 AN: 5768

European-Non Finnish (NFE) AF: 0.00838 AC: 9316 AN: 1111988

Other (OTH) AF: 0.00541 AC: 327 AN: 60392

GnomAD4 genome AF: 0.00449 AC: 684 AN: 152260 Hom.: 6 Cov.: 32 AF XY: 0.00442 AC XY: 329 AN XY: 74450

African (AFR) AF: 0.00159 AC: 66 AN: 41548

American (AMR) AF: 0.00478 AC: 73 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00260 AC: 9 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00187 AC: 9 AN: 4824

European-Finnish (FIN) AF: 0.00160 AC: 17 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00740 AC: 503 AN: 68014

Other (OTH) AF: 0.00331 AC: 7 AN: 2116

Alfa AF: 0.00587 Hom.: 8

Bravo AF: 0.00475

TwinsUK AF: 0.00782 AC: 29

ALSPAC AF: 0.00701 AC: 27

ESP6500AA AF: 0.00218 AC: 8

ESP6500EA AF: 0.00785 AC: 64

ExAC AF: 0.00500 AC: 604

EpiCase AF: 0.00703

EpiControl AF: 0.00871

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	0.11
BayesDel_addAF	Benign	-0.50	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	13
DANN	Benign	0.94
DEOGEN2	Benign	0.032	T
Eigen	Benign	-0.72
Eigen_PC	Benign	-0.62
FATHMM_MKL	Benign	0.38	N
LIST_S2	Benign	0.38	T
M_CAP	Benign	0.0092	T
MetaRNN	Benign	0.0051	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		3.0
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.95	N
REVEL	Benign	0.061
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.0070	D
Polyphen		0.12	B
Vest4		0.12
MVP		0.048
MPC		0.13
ClinPred		0.015	T
GERP RS		4.3
Varity_R		0.10
gMVP		0.16
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs188950262; hg19: chr11-32635096; COSMIC: COSV100068600; COSMIC: COSV100068600;