rs768663992

Positions:

• chr16-3508407-T-C
• chr16-3508407-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM2 PM5 BP4_Moderate

The NM_015041.3(CLUAP1):​c.338T>C​(p.Met113Thr) 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. 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. M113R) has been classified as Likely pathogenic.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CLUAP1 NM_015041.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.24

Genes affected

CLUAP1 (HGNC:19009): (clusterin associated protein 1) The protein encoded by this gene contains a single coiled-coil region. Alternative splicing results in multiple transcript variants and protein isoforms. [provided by RefSeq, Jul 2012]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM5: Other missense variant is known to change same aminoacid residue: Variant chr16-3508407-T-G is described in ClinVar as [Likely_pathogenic]. Clinvar id is 254179.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP4: Computational evidence support a benign effect (MetaRNN=0.102725655).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CLUAP1	NM_015041.3	c.338T>C	p.Met113Thr	missense_variant	4/12	ENST00000576634.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CLUAP1	ENST00000576634.6	c.338T>C	p.Met113Thr	missense_variant	4/12	1	NM_015041.3	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	16
DANN	Benign	0.70
DEOGEN2	Benign	0.0044	T;.;.;T
Eigen	Benign	-0.39
Eigen_PC	Benign	-0.19
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.78	T;T;T;T
M_CAP	Benign	0.0088	T
MetaRNN	Benign	0.10	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.34	N;.;.;.
MutationTaster	Benign	0.83	D;D;D;D
PrimateAI	Benign	0.47	T
PROVEAN	Benign	0.19	.;N;.;.
REVEL	Benign	0.078
Sift	Benign	0.62	.;T;.;.
Sift4G	Benign	0.62	T;T;T;T
Polyphen		0.0010	B;.;.;.
Vest4		0.39
MutPred		0.34		Loss of methylation at K111 (P = 0.0598);Loss of methylation at K111 (P = 0.0598);Loss of methylation at K111 (P = 0.0598);.;
MVP		0.34
MPC		0.053
ClinPred		0.41	T
GERP RS		4.9
Varity_R		0.13
gMVP		0.25

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

Other links and lift over

dbSNP: rs768663992; hg19: chr16-3558407;