10-104132169-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_025145.7(CFAP43):c.4624C>G(p.Leu1542Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.008 in 1,603,012 control chromosomes in the GnomAD database, including 72 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0069 (14 hom., cov: 32)
  • Exomes 𝑓: 0.0081 (58 hom.)
• Consequence: CFAP43 NM_025145.7 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.209

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0041635334).
• BP6: Variant 10-104132169-G-C is Benign according to our data. Variant chr10-104132169-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 709932.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00685 (1042/152012) while in subpopulation NFE AF= 0.0104 (706/67982). AF 95% confidence interval is 0.00975. There are 14 homozygotes in gnomad4. There are 544 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 14 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CFAP43	NM_025145.7	c.4624C>G	p.Leu1542Val	missense_variant	36/38	ENST00000357060.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CFAP43	ENST00000357060.8	c.4624C>G	p.Leu1542Val	missense_variant	36/38	1	NM_025145.7	P1
CFAP43	ENST00000434629.5	c.2620C>G	p.Leu874Val	missense_variant	21/23	1
CFAP43	ENST00000457071.5	c.1171C>G	p.Leu391Val	missense_variant	10/12	2

Frequencies

GnomAD3 genomes AF: 0.00687 AC: 1043 AN: 151894 Hom.: 14 Cov.: 32

Gnomad AFR AF: 0.00152

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00302

Gnomad ASJ AF: 0.00576

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.0185

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0104

Gnomad OTH AF: 0.00480

GnomAD3 exomes AF: 0.00608 AC: 1478 AN: 242960 Hom.: 4 AF XY: 0.00609 AC XY: 798 AN XY: 131136

Gnomad AFR exome AF: 0.00131

Gnomad AMR exome AF: 0.00176

Gnomad ASJ exome AF: 0.00404

Gnomad EAS exome AF: 0.0000558

Gnomad SAS exome AF: 0.00139

Gnomad FIN exome AF: 0.0149

Gnomad NFE exome AF: 0.00869

Gnomad OTH exome AF: 0.00585

GnomAD4 exome AF: 0.00812 AC: 11781 AN: 1451000 Hom.: 58 Cov.: 29 AF XY: 0.00799 AC XY: 5767 AN XY: 721348

Gnomad4 AFR exome AF: 0.00118

Gnomad4 AMR exome AF: 0.00189

Gnomad4 ASJ exome AF: 0.00382

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00120

Gnomad4 FIN exome AF: 0.0144

Gnomad4 NFE exome AF: 0.00926

Gnomad4 OTH exome AF: 0.00699

GnomAD4 genome AF: 0.00685 AC: 1042 AN: 152012 Hom.: 14 Cov.: 32 AF XY: 0.00732 AC XY: 544 AN XY: 74284

Gnomad4 AFR AF: 0.00152

Gnomad4 AMR AF: 0.00295

Gnomad4 ASJ AF: 0.00576

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000416

Gnomad4 FIN AF: 0.0185

Gnomad4 NFE AF: 0.0104

Gnomad4 OTH AF: 0.00475

Alfa AF: 0.00950 Hom.: 8

Bravo AF: 0.00486

TwinsUK AF: 0.00863 AC: 32

ALSPAC AF: 0.00908 AC: 35

ESP6500AA AF: 0.00136 AC: 6

ESP6500EA AF: 0.00978 AC: 84

ExAC AF: 0.00589 AC: 715

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jan 01, 2024	CFAP43: BP4, BS2 -
Benign, criteria provided, single submitter	clinical testing	Invitae	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.64	T
BayesDel_noAF	Benign	-0.68
Cadd	Benign	1.6
Dann	Benign	0.79
DEOGEN2	Benign	0.039	T
Eigen	Benign	-0.91
Eigen_PC	Benign	-0.87
FATHMM_MKL	Benign	0.049	N
LIST_S2	Benign	0.59	T
MetaRNN	Benign	0.0042	T
MetaSVM	Benign	-0.96	T
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.92	N
REVEL	Benign	0.078
Sift	Benign	0.53	T
Sift4G	Benign	0.54	T
Polyphen		0.016	B
Vest4		0.059
MVP		0.17
MPC		0.14
ClinPred		0.0012	T
GERP RS		1.6
Varity_R		0.055
gMVP		0.11

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: rs117628923; hg19: chr10-105891927; COSMIC: COSV63853160; COSMIC: COSV63853160;