Genetic Variant NM_001258306.3:c.50C>T (chr2-131528020-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001258306.3(CCDC74A):c.50C>T(p.Thr17Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000169 in 1,483,248 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000092 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000083 ( 0 hom. )

Consequence

CCDC74A
NM_001258306.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.337

Publications

0 publications found

Variant links:

Genes affected

CCDC74A (HGNC:25197): (coiled-coil domain containing 74A)

CCDC74A links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.017751455).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001258306.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CCDC74A	NM_001258306.3	MANE Select	c.50C>T	p.Thr17Ile	missense	Exon 1 of 8	NP_001245235.1	Q96AQ1-2
CCDC74A	NM_001349042.2		c.50C>T	p.Thr17Ile	missense	Exon 1 of 8	NP_001335971.1
CCDC74A	NM_138770.4		c.50C>T	p.Thr17Ile	missense	Exon 1 of 8	NP_620125.1	Q96AQ1-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CCDC74A	ENST00000409856.8	TSL:1 MANE Select	c.50C>T	p.Thr17Ile	missense	Exon 1 of 8	ENSP00000387009.3	Q96AQ1-2
CCDC74A	ENST00000295171.10	TSL:1	c.50C>T	p.Thr17Ile	missense	Exon 1 of 8	ENSP00000295171.6	Q96AQ1-1
CCDC74A	ENST00000467992.6	TSL:1	c.50C>T	p.Thr17Ile	missense	Exon 1 of 7	ENSP00000444610.2	F5GZA4

Frequencies

GnomAD3 genomes

AF:

0.0000922

AC:

AN:

151818

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000314

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000417

AC:

AN:

95872

AF XY:

0.0000589

show subpopulations

Gnomad AFR exome

AF:

0.000566

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000826

AC:

AN:

1331430

Hom.:

Cov.:

AF XY:

0.00000768

AC XY:

AN XY:

650872

show subpopulations

African (AFR)

AF:

0.000306

AC:

AN:

29430

American (AMR)

AF:

0.00

AC:

AN:

22508

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20136

East Asian (EAS)

AF:

0.00

AC:

AN:

36130

South Asian (SAS)

AF:

0.0000148

AC:

AN:

67642

European-Finnish (FIN)

AF:

0.00

AC:

AN:

45642

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3778

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1051368

Other (OTH)

AF:

0.0000182

AC:

AN:

54796

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

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

AF:

0.0000922

AC:

AN:

151818

Hom.:

Cov.:

AF XY:

0.0000944

AC XY:

AN XY:

74138

show subpopulations

African (AFR)

AF:

0.000314

AC:

AN:

41360

American (AMR)

AF:

0.0000655

AC:

AN:

15260

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5118

South Asian (SAS)

AF:

0.00

AC:

AN:

4808

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10610

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67890

Other (OTH)

AF:

0.00

AC:

AN:

2076

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.000102

ExAC

AF:

0.0000365

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.22

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.71

CADD

Benign

4.0

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0025

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.016

LIST_S2

Benign

0.65

M_CAP

Benign

0.0097

MetaRNN

Benign

0.018

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.26

PhyloP100

-0.34

PrimateAI

Pathogenic

0.82

PROVEAN

Benign

-1.0

REVEL

Benign

0.023

Sift

Benign

0.16

Sift4G

Benign

0.11

Polyphen

0.0030

Vest4

0.074

MutPred

0.22

Loss of phosphorylation at T17 (P = 0.0013)

MVP

0.040

MPC

1.7

ClinPred

0.025

GERP RS

0.19

PromoterAI

0.012

Neutral

(source)

Varity_R

0.052

gMVP

0.093

Mutation Taster

=96/4

polymorphism

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over