chr11-22860397-C-G

Position:

• chr11-22860397-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001195637.2(CCDC179):​c.25G>C​(p.Glu9Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000145 in 1,383,268 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: CCDC179 NM_001195637.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.65

Genes affected

CCDC179 (HGNC:44653): (coiled-coil domain containing 179)

(HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19480556).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC179	NM_001195637.2	c.25G>C	p.Glu9Gln	missense_variant	1/4	ENST00000532798.3	NP_001182566.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC179	ENST00000532798.3	c.25G>C	p.Glu9Gln	missense_variant	1/4	2	NM_001195637.2	ENSP00000457511	P1
	ENST00000499625.1	n.484+22033C>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000749 AC: 1 AN: 133574 Hom.: 0 AF XY: 0.0000137 AC XY: 1 AN XY: 72748

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000413

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000145 AC: 2 AN: 1383268 Hom.: 0 Cov.: 31 AF XY: 0.00000293 AC XY: 2 AN XY: 682590

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000281

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000280

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Bladder exstrophy-epispadias-cloacal extrophy complex Uncertain:1

Uncertain significance, criteria provided, single submitter

curation

Obstetrics and Gynecology Department, Johns Hopkins School Of Medicine

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	18
DANN	Benign	0.73
DEOGEN2	Benign	0.051	T
FATHMM_MKL	Benign	0.18	N
LIST_S2	Benign	0.44	T
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.19	T
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.39	T
PROVEAN	Uncertain	-2.7	D
Sift	Benign	0.038	D
Sift4G	Benign	0.080	T
Vest4		0.35
MVP		0.081
GERP RS		3.2
Varity_R		0.13
gMVP		0.020

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

Publications

LitVar

Other links and lift over

dbSNP: rs757673440; hg19: chr11-22881943;