chr12-28452604-G-T

Position:

• chr12-28452604-G-T

Variant summary

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

The NM_018318.5(CCDC91):​c.1051G>T​(p.Val351Leu) 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: CCDC91 NM_018318.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.02

Genes affected

CCDC91 (HGNC:24855): (coiled-coil domain containing 91) Predicted to enable identical protein binding activity. Involved in Golgi to lysosome transport. Located in nucleoplasm and trans-Golgi network. [provided by Alliance of Genome Resources, Apr 2022]

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=0.089826286).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC91	NM_018318.5	c.1051G>T	p.Val351Leu	missense_variant	11/13	ENST00000536442.6	NP_060788.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC91	ENST00000536442.6	c.1051G>T	p.Val351Leu	missense_variant	11/13	5	NM_018318.5	ENSP00000445660	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 19, 2024

The c.1051G>T (p.V351L) alteration is located in exon 10 (coding exon 10) of the CCDC91 gene. This alteration results from a G to T substitution at nucleotide position 1051, causing the valine (V) at amino acid position 351 to be replaced by a leucine (L). 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	0.24
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	16
DANN	Benign	0.96
DEOGEN2	Benign	0.035	T;.;T;T;.
Eigen	Benign	-0.28
Eigen_PC	Benign	-0.094
FATHMM_MKL	Benign	0.65	D
LIST_S2	Uncertain	0.88	D;D;.;D;D
M_CAP	Benign	0.0076	T
MetaRNN	Benign	0.090	T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.69	.;.;N;N;.
MutationTaster	Benign	1.0	N;N;N;N;N
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-1.7	N;N;N;N;N
REVEL	Benign	0.040
Sift	Uncertain	0.017	D;T;T;T;D
Sift4G	Benign	0.38	T;T;T;T;T
Polyphen		0.50, 0.011	.;P;B;B;.
Vest4		0.14, 0.14, 0.11
MutPred		0.24		.;.;Loss of methylation at K350 (P = 0.0375);Loss of methylation at K350 (P = 0.0375);.;
MVP		0.28
MPC		0.077
ClinPred		0.49	T
GERP RS		3.6
Varity_R		0.040
gMVP		0.051

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: chr12-28605537;