chr12-121923696-C-T

Variant names:

• chr12-121923696-C-T
• rs189409230
• NM_144668.6:c.453C>T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6 BP7

The NM_144668.6(CFAP251):​c.453C>T​(p.Asp151Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000538 in 1,614,106 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.00034 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00056 (0 hom.)
• Consequence: CFAP251 NM_144668.6 synonymous
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.837
• Publications: 1 publications found

Genes affected

CFAP251 (HGNC:28506): (cilia and flagella associated protein 251) This protein encoded by this gene belongs to the WD repeat-containing family of proteins, which function in the formation of protein-protein complexes in a variety of biological pathways. This family member appears to function in the determination of mean platelet volume (MPV), and polymorphisms in this gene have been associated with variance in MPV. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Sep 2011]

CFAP251 Gene-Disease associations (from GenCC):

• spermatogenic failure 33

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• non-syndromic male infertility due to sperm motility disorder

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 12-121923696-C-T is Benign according to our data. Variant chr12-121923696-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3049348.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=-0.837 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_144668.6. 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
	CFAP251	NM_144668.6	MANE Select	c.453C>T	p.Asp151Asp	synonymous	Exon 3 of 22	NP_653269.3	Q8TBY9-1
	CFAP251	NM_001178003.2		c.453C>T	p.Asp151Asp	synonymous	Exon 3 of 18	NP_001171474.1	Q8TBY9-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFAP251	ENST00000288912.9	TSL:1 MANE Select	c.453C>T	p.Asp151Asp	synonymous	Exon 3 of 22	ENSP00000288912.4	Q8TBY9-1
	CFAP251	ENST00000397454.2	TSL:1	c.453C>T	p.Asp151Asp	synonymous	Exon 3 of 18	ENSP00000380595.2	Q8TBY9-2
	CFAP251	ENST00000880754.1		c.453C>T	p.Asp151Asp	synonymous	Exon 3 of 22	ENSP00000550813.1

Frequencies

GnomAD3 genomes AF: 0.000342 AC: 52 AN: 152100 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000656

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000676

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000284 AC: 71 AN: 249566 AF XY: 0.000288

Gnomad AFR exome AF: 0.000323

Gnomad AMR exome AF: 0.0000579

Gnomad ASJ exome AF: 0.000199

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000538

Gnomad OTH exome AF: 0.000165

GnomAD4 exome AF: 0.000558 AC: 816 AN: 1461888 Hom.: 0 Cov.: 31 AF XY: 0.000567 AC XY: 412 AN XY: 727246

African (AFR) AF: 0.000388 AC: 13 AN: 33480

American (AMR) AF: 0.000157 AC: 7 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.000115 AC: 3 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5768

European-Non Finnish (NFE) AF: 0.000696 AC: 774 AN: 1112010

Other (OTH) AF: 0.000298 AC: 18 AN: 60394

GnomAD4 genome AF: 0.000342 AC: 52 AN: 152218 Hom.: 1 Cov.: 32 AF XY: 0.000161 AC XY: 12 AN XY: 74422

African (AFR) AF: 0.000120 AC: 5 AN: 41512

American (AMR) AF: 0.0000655 AC: 1 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000676 AC: 46 AN: 68022

Other (OTH) AF: 0.00 AC: 0 AN: 2110

Alfa AF: 0.000654 Hom.: 0

Bravo AF: 0.000385

EpiCase AF: 0.000927

EpiControl AF: 0.00101

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	CFAP251-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.53
DANN	Benign	0.25
PhyloP100		-0.84
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs189409230; hg19: chr12-122361602;