Genetic Variant CCDC171:p.Ala61Thr (chr9-15578852-G-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_173550.4(CCDC171):c.181G>A(p.Ala61Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,458,586 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. A61S) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

CCDC171
NM_173550.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.19

Publications

2 publications found

Variant links:

Genes affected

CCDC171 (HGNC:29828): (coiled-coil domain containing 171)

CCDC171 links:

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ACMG classification

Classification was made for transcript

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=0.054933697).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173550.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CCDC171	NM_173550.4	MANE Select	c.181G>A	p.Ala61Thr	missense	Exon 4 of 26	NP_775821.2
CCDC171	NM_001355547.1		c.181G>A	p.Ala61Thr	missense	Exon 3 of 25	NP_001342476.1	Q6TFL3-4
CCDC171	NM_001348002.2		c.-261G>A		5_prime_UTR	Exon 4 of 27	NP_001334931.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CCDC171	ENST00000380701.8	TSL:1 MANE Select	c.181G>A	p.Ala61Thr	missense	Exon 4 of 26	ENSP00000370077.3	Q6TFL3-1
CCDC171	ENST00000905141.1		c.181G>A	p.Ala61Thr	missense	Exon 4 of 26	ENSP00000575200.1
CCDC171	ENST00000971281.1		c.181G>A	p.Ala61Thr	missense	Exon 4 of 26	ENSP00000641340.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000403

AC:

AN:

248436

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000888

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000206

AC:

AN:

1458586

Hom.:

Cov.:

AF XY:

0.00000276

AC XY:

AN XY:

725584

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33294

American (AMR)

AF:

0.00

AC:

AN:

44164

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26002

East Asian (EAS)

AF:

0.00

AC:

AN:

39544

South Asian (SAS)

AF:

0.00

AC:

AN:

85772

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53336

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5746

European-Non Finnish (NFE)

AF:

0.00000270

AC:

AN:

1110508

Other (OTH)

AF:

0.00

AC:

AN:

60220

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.392

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000225

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.70

CADD

Benign

(source)

DANN

Benign

0.87

DEOGEN2

Benign

0.020

Eigen

Benign

-0.61

Eigen_PC

Benign

-0.44

FATHMM_MKL

Benign

0.49

LIST_S2

Benign

0.75

M_CAP

Benign

0.0044

MetaRNN

Benign

0.055

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.76

PhyloP100

1.2

PrimateAI

Benign

0.34

PROVEAN

Benign

-0.10

REVEL

Benign

0.040

Sift

Benign

0.42

Sift4G

Benign

0.61

Polyphen

0.0

Vest4

0.18

MutPred

0.093

Gain of phosphorylation at A61 (P = 0.0685)

MVP

0.030

ClinPred

0.046

GERP RS

1.6

Varity_R

0.029

gMVP

0.021

Mutation Taster

=98/2

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over