rs1684601328

Variant names:

• chr2-158176618-T-A
• rs1684601328
• NM_138803.4:c.1532A>T

Variant summary

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

The NM_138803.4(CCDC148):​c.1532A>T​(p.Asp511Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CCDC148 NM_138803.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.12

Genes affected

CCDC148 (HGNC:25191): (coiled-coil domain containing 148)

CCDC148-AS1 (HGNC:44134): (CCDC148 antisense RNA 1)

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC148	NM_138803.4	c.1532A>T	p.Asp511Val	missense_variant	Exon 13 of 14	ENST00000283233.10	NP_620158.3
CCDC148	NM_001301684.2	c.1094A>T	p.Asp365Val	missense_variant	Exon 11 of 12		NP_001288613.1
CCDC148-AS1	NR_038850.1	n.92T>A		non_coding_transcript_exon_variant	Exon 2 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC148	ENST00000283233.10	c.1532A>T	p.Asp511Val	missense_variant	Exon 13 of 14	1	NM_138803.4	ENSP00000283233.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jun 28, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1532A>T (p.D511V) alteration is located in exon 13 (coding exon 13) of the CCDC148 gene. This alteration results from a A to T substitution at nucleotide position 1532, causing the aspartic acid (D) at amino acid position 511 to be replaced by a valine (V). 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	0.33
BayesDel_addAF	Uncertain	0.073	D
BayesDel_noAF	Benign	-0.13
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.077	T;.
Eigen	Uncertain	0.55
Eigen_PC	Uncertain	0.57
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.85	T;T
M_CAP	Benign	0.043	D
MetaRNN	Uncertain	0.59	D;D
MetaSVM	Benign	-0.98	T
MutationAssessor	Uncertain	2.6	M;.
PrimateAI	Uncertain	0.49	T
PROVEAN	Uncertain	-4.1	D;D
REVEL	Benign	0.20
Sift	Uncertain	0.0050	D;D
Sift4G	Uncertain	0.0050	D;D
Polyphen		0.99	D;D
Vest4		0.78
MutPred		0.30		.;Loss of disorder (P = 0.0283);
MVP		0.44
MPC		0.082
ClinPred		0.98	D
GERP RS		5.8
Varity_R		0.38
gMVP		0.52

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: rs1684601328; hg19: chr2-159033130;