NM_025059.4:c.12C>T

Variant names:

• chr6-151494140-C-T
• rs372621574
• NM_025059.4:c.12C>T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_025059.4(CCDC170):​c.12C>T​(p.Asp4Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000735 in 1,361,288 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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: 7.3e-7 (0 hom.)
• Consequence: CCDC170 NM_025059.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.985
• Publications: 0 publications found

Genes affected

CCDC170 (HGNC:21177): (coiled-coil domain containing 170) The function of this gene and its encoded protein is not known. Several genome-wide association studies have implicated the region around this gene to be involved in breast cancer and bone mineral density, but no link to this specific gene has been found. [provided by RefSeq, May 2010]

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BP7: Synonymous conserved (PhyloP=-0.985 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_025059.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC170	NM_025059.4	MANE Select	c.12C>T	p.Asp4Asp	synonymous	Exon 1 of 11	NP_079335.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC170	ENST00000239374.8	TSL:1 MANE Select	c.12C>T	p.Asp4Asp	synonymous	Exon 1 of 11	ENSP00000239374.6	Q8IYT3
	CCDC170	ENST00000867015.1		c.12C>T	p.Asp4Asp	synonymous	Exon 1 of 11	ENSP00000537074.1
	CCDC170	ENST00000867016.1		c.12C>T	p.Asp4Asp	synonymous	Exon 1 of 10	ENSP00000537075.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.35e-7 AC: 1 AN: 1361288 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 672058

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 28302

American (AMR) AF: 0.00 AC: 0 AN: 31886

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24198

East Asian (EAS) AF: 0.00 AC: 0 AN: 31008

South Asian (SAS) AF: 0.00 AC: 0 AN: 76156

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40036

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4736

European-Non Finnish (NFE) AF: 9.36e-7 AC: 1 AN: 1068404

Other (OTH) AF: 0.00 AC: 0 AN: 56562

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	4.5
DANN	Benign	0.93
PhyloP100		-0.98
PromoterAI		0.12	Neutral

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: rs372621574; hg19: chr6-151815275;