3-119715573-A-T

Position:

• chr3-119715573-A-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_033364.4(CFAP91):​c.512A>T​(p.Tyr171Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000197 in 152,204 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: 𝑓 0.000020 (0 hom., cov: 32)
• Consequence: CFAP91 NM_033364.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.376

Genes affected

CFAP91 (HGNC:24010): (cilia and flagella associated protein 91) Predicted to be involved in cilium movement. Predicted to be located in axoneme and motile cilium. Predicted to colocalize with radial spoke stalk. Implicated in spermatogenic failure 51. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000285585 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05897203).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CFAP91	NM_033364.4	c.512A>T	p.Tyr171Phe	missense_variant	6/18	ENST00000273390.9	NP_203528.3
CFAP91	NM_001320316.2	c.452A>T	p.Tyr151Phe	missense_variant	6/18		NP_001307245.2
CFAP91	NM_001320317.2	c.326A>T	p.Tyr109Phe	missense_variant	5/17		NP_001307246.2
CFAP91	NM_001320318.2	c.134A>T	p.Tyr45Phe	missense_variant	4/16		NP_001307247.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CFAP91	ENST00000273390.9	c.512A>T	p.Tyr171Phe	missense_variant	6/18	1	NM_033364.4	ENSP00000273390.5
ENSG00000285585	ENST00000648112.1	c.512A>T	p.Tyr171Phe	missense_variant	6/18			ENSP00000497876.1

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152204 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 30

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152204 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74348

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.000196

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Bravo AF: 0.0000151

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 22, 2023

The c.512A>T (p.Y171F) alteration is located in exon 6 (coding exon 6) of the MAATS1 gene. This alteration results from a A to T substitution at nucleotide position 512, causing the tyrosine (Y) at amino acid position 171 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.082
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	7.1
DANN	Benign	0.72
DEOGEN2	Benign	0.0020	T;.;.
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.052	N
LIST_S2	Benign	0.70	.;T;T
M_CAP	Benign	0.0022	T
MetaRNN	Benign	0.059	T;T;T
MetaSVM	Benign	-1.1	T
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.47	N;N;.
REVEL	Benign	0.050
Sift	Benign	0.51	T;T;.
Sift4G	Benign	0.63	T;T;.
Polyphen		0.027	B;B;.
Vest4		0.14
MutPred		0.28		Loss of phosphorylation at Y171 (P = 0.028);Loss of phosphorylation at Y171 (P = 0.028);Loss of phosphorylation at Y171 (P = 0.028);
MVP		0.055
MPC		0.12
ClinPred		0.044	T
GERP RS		-3.0
Varity_R		0.053
gMVP		0.17

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs951168502; hg19: chr3-119434420;