chr1-169395103-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001300969.2(CCDC181):​c.1474C>T​(p.His492Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000186 in 1,613,440 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

CCDC181
NM_001300969.2 missense

Scores

19

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.835
Variant links:
Genes affected
CCDC181 (HGNC:28051): (coiled-coil domain containing 181) Predicted to enable microtubule binding activity. Predicted to be located in manchette and sperm flagellum. [provided by Alliance of Genome Resources, Apr 2022]
BLZF1 (HGNC:1065): (basic leucine zipper nuclear factor 1) Enables ubiquitin protein ligase binding activity. Acts upstream of or within Golgi organization and Golgi to plasma membrane protein transport. Located in Golgi apparatus and nucleoplasm. Biomarker of hepatocellular carcinoma. [provided by Alliance of Genome Resources, Apr 2022]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.03923288).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CCDC181NM_001300969.2 linkuse as main transcriptc.1474C>T p.His492Tyr missense_variant 6/6 ENST00000367806.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CCDC181ENST00000367806.8 linkuse as main transcriptc.1474C>T p.His492Tyr missense_variant 6/61 NM_001300969.2 A1Q5TID7-1
CCDC181ENST00000367805.7 linkuse as main transcriptc.1471C>T p.His491Tyr missense_variant 6/61 P4Q5TID7-3
CCDC181ENST00000545005.5 linkuse as main transcriptc.1471C>T p.His491Tyr missense_variant 7/71 P4Q5TID7-3
BLZF1ENST00000329281.6 linkuse as main transcriptc.*28-791G>A intron_variant 1 P1Q9H2G9-1

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152212
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
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:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000399
AC:
1
AN:
250628
Hom.:
0
AF XY:
0.00000738
AC XY:
1
AN XY:
135488
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 SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000881
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1461228
Hom.:
0
Cov.:
31
AF XY:
0.00000138
AC XY:
1
AN XY:
726916
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000180
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152212
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74364
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.078
BayesDel_addAF
Benign
-0.32
T
BayesDel_noAF
Benign
-0.69
CADD
Benign
17
DANN
Benign
0.95
DEOGEN2
Benign
0.0089
T;.;.
Eigen
Benign
-0.97
Eigen_PC
Benign
-0.87
FATHMM_MKL
Benign
0.25
N
LIST_S2
Benign
0.52
T;.;T
M_CAP
Benign
0.0036
T
MetaRNN
Benign
0.039
T;T;T
MetaSVM
Benign
-0.94
T
MutationAssessor
Benign
0.0
N;.;.
MutationTaster
Benign
1.0
D;N;N;N
PrimateAI
Benign
0.29
T
PROVEAN
Benign
-1.4
N;N;N
REVEL
Benign
0.020
Sift
Benign
0.17
T;T;T
Sift4G
Benign
0.45
T;T;T
Polyphen
0.0
B;B;B
Vest4
0.078
MutPred
0.28
Gain of phosphorylation at H492 (P = 0.0276);.;.;
MVP
0.030
MPC
0.12
ClinPred
0.035
T
GERP RS
-0.85
Varity_R
0.048
gMVP
0.060

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1226003386; hg19: chr1-169364341; API