chr3-49163425-T-A

Variant summary

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

The NM_022903.4(CCDC71):​c.784A>T​(p.Thr262Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)

Consequence

CCDC71
NM_022903.4 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.176
Variant links:
Genes affected
CCDC71 (HGNC:25760): (coiled-coil domain containing 71) Predicted to be involved in cellular lipid metabolic process and positive regulation of fat cell differentiation. [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=0.033302784).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
CCDC71NM_022903.4 linkuse as main transcriptc.784A>T p.Thr262Ser missense_variant 2/2 ENST00000321895.7 NP_075054.3 Q8IV32

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CCDC71ENST00000321895.7 linkuse as main transcriptc.784A>T p.Thr262Ser missense_variant 2/21 NM_022903.4 ENSP00000319006.6 Q8IV32

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
34
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsMar 14, 2023The c.784A>T (p.T262S) alteration is located in exon 2 (coding exon 1) of the CCDC71 gene. This alteration results from a A to T substitution at nucleotide position 784, causing the threonine (T) at amino acid position 262 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.091
BayesDel_addAF
Benign
-0.30
T
BayesDel_noAF
Benign
-0.67
CADD
Benign
0.51
DANN
Benign
0.32
DEOGEN2
Benign
0.0025
T
Eigen
Benign
-1.0
Eigen_PC
Benign
-1.0
FATHMM_MKL
Benign
0.14
N
LIST_S2
Benign
0.29
T
M_CAP
Benign
0.0063
T
MetaRNN
Benign
0.033
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.1
L
MutationTaster
Benign
1.0
N
PrimateAI
Benign
0.39
T
PROVEAN
Benign
0.10
N
REVEL
Benign
0.016
Sift
Benign
0.57
T
Sift4G
Benign
0.64
T
Polyphen
0.0010
B
Vest4
0.092
MutPred
0.15
Gain of methylation at R260 (P = 0.1137);
MVP
0.19
MPC
0.15
ClinPred
0.054
T
GERP RS
-0.69
Varity_R
0.069
gMVP
0.084

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-49200858; API