2-158340259-T-G

Variant names:

• chr2-158340259-T-G
• rs12620556
• NM_138803.4:c.469A>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_138803.4(CCDC148):​c.469A>C​(p.Met157Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,452 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: CCDC148 NM_138803.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.279
• Publications: 0 publications found

Genes affected

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

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04907465).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138803.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC148	NM_138803.4	MANE Select	c.469A>C	p.Met157Leu	missense	Exon 5 of 14	NP_620158.3
	CCDC148	NM_001301685.2		c.469A>C	p.Met157Leu	missense	Exon 5 of 7	NP_001288614.1
	CCDC148	NM_001301684.2		c.48+339A>C		intron	N/A	NP_001288613.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC148	ENST00000283233.10	TSL:1 MANE Select	c.469A>C	p.Met157Leu	missense	Exon 5 of 14	ENSP00000283233.5
	CCDC148	ENST00000409889.1	TSL:1	c.469A>C	p.Met157Leu	missense	Exon 5 of 7	ENSP00000386583.1
	CCDC148	ENST00000417066.5	TSL:1	n.*195A>C		non_coding_transcript_exon	Exon 3 of 8	ENSP00000400751.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461452 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727052

African (AFR) AF: 0.00 AC: 0 AN: 33456

American (AMR) AF: 0.00 AC: 0 AN: 44664

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26124

East Asian (EAS) AF: 0.00 AC: 0 AN: 39636

South Asian (SAS) AF: 0.00 AC: 0 AN: 86230

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53382

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111824

Other (OTH) AF: 0.00 AC: 0 AN: 60374

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.093
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.17
DANN	Benign	0.40
DEOGEN2	Benign	0.00036	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.022	N
LIST_S2	Benign	0.31	T
M_CAP	Benign	0.0053	T
MetaRNN	Benign	0.049	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		-0.28
PrimateAI	Benign	0.26	T
PROVEAN	Benign	0.090	N
REVEL	Benign	0.014
Sift	Benign	0.31	T
Sift4G	Benign	0.31	T
Polyphen		0.0	B
Vest4		0.036
MutPred		0.22		Loss of ubiquitination at K158 (P = 0.0715)
MVP		0.067
MPC		0.012
ClinPred		0.047	T
GERP RS		-2.0
Varity_R		0.054
gMVP		0.083
Mutation Taster		=98/2	polymorphism

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

Other links and lift over

dbSNP: rs12620556; hg19: chr2-159196771;