10-104143450-T-G

Variant names:

• chr10-104143450-T-G
• rs201272158
• NM_025145.7:c.4134A>C
• CFAP43 p.Arg1378Arg

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Moderate BP6 BP7

The NM_025145.7(CFAP43):​c.4134A>C​(p.Arg1378Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000248 in 1,613,994 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000027 (0 hom.)
• Consequence: CFAP43 NM_025145.7 synonymous
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 3.38
• Publications: 0 publications found

Genes affected

CFAP43 (HGNC:26684): (cilia and flagella associated protein 43) This gene encodes a member of the cilia- and flagella-associated protein family. [provided by RefSeq, Sep 2016]

CFAP43 Gene-Disease associations (from GenCC):

• spermatogenic failure 19

  Inheritance: AR Classification: DEFINITIVE, LIMITED Submitted by: ClinGen, Ambry Genetics
• non-syndromic male infertility due to sperm motility disorder

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• normal pressure hydrocephalus

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen, Ambry Genetics
• primary ciliary dyskinesia

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: ClinGen

ENSG00000294028 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.08).
• BP6: Variant 10-104143450-T-G is Benign according to our data. Variant chr10-104143450-T-G is described in ClinVar as Likely_benign. ClinVar VariationId is 3034143.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=3.38 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_025145.7. 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
	CFAP43	NM_025145.7	MANE Select	c.4134A>C	p.Arg1378Arg	synonymous	Exon 32 of 38	NP_079421.5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFAP43	ENST00000357060.8	TSL:1 MANE Select	c.4134A>C	p.Arg1378Arg	synonymous	Exon 32 of 38	ENSP00000349568.3	Q8NDM7-1
	CFAP43	ENST00000434629.5	TSL:1	c.2127A>C	p.Arg709Arg	synonymous	Exon 17 of 23	ENSP00000391364.1	H7BZT8
	CFAP43	ENST00000457071.5	TSL:2	c.678A>C	p.Arg226Arg	synonymous	Exon 6 of 12	ENSP00000394274.1	H0Y4U9

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152246 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000119 AC: 3 AN: 251082 AF XY: 0.00

Gnomad AFR exome AF: 0.0000615

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000267 AC: 39 AN: 1461748 Hom.: 0 Cov.: 31 AF XY: 0.0000344 AC XY: 25 AN XY: 727164

African (AFR) AF: 0.0000299 AC: 1 AN: 33476

American (AMR) AF: 0.00 AC: 0 AN: 44690

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86220

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53404

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.0000324 AC: 36 AN: 1111980

Other (OTH) AF: 0.0000331 AC: 2 AN: 60388

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152246 Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1 AN XY: 74370

African (AFR) AF: 0.00 AC: 0 AN: 41466

American (AMR) AF: 0.00 AC: 0 AN: 15286

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5202

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68044

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.0000282 Hom.: 0

Bravo AF: 0.00000756

EpiCase AF: 0.000109

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	CFAP43-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	6.9
DANN	Benign	0.50
PhyloP100		3.4

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs201272158;

hg19: chr10-105903208;