1-32361817-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001167676.2(FAM229A):ā€‹c.194T>Cā€‹(p.Ile65Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000165 in 1,329,640 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: š‘“ 0.000046 ( 0 hom., cov: 32)
Exomes š‘“: 0.000013 ( 0 hom. )

Consequence

FAM229A
NM_001167676.2 missense

Scores

4
4
7

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.95
Variant links:
Genes affected
FAM229A (HGNC:44652): (family with sequence similarity 229 member A)
TSSK3 (HGNC:15473): (testis specific serine kinase 3) This gene encodes a kinase expressed exclusively in the testis that is thought to play a role in either germ cell differentiation or mature sperm function. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
FAM229ANM_001167676.2 linkuse as main transcriptc.194T>C p.Ile65Thr missense_variant 2/3 ENST00000432622.2 NP_001161148.1 H3BQW9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
FAM229AENST00000432622.2 linkuse as main transcriptc.194T>C p.Ile65Thr missense_variant 2/32 NM_001167676.2 ENSP00000455971.1 H3BQW9

Frequencies

GnomAD3 genomes
AF:
0.0000461
AC:
7
AN:
151994
Hom.:
0
Cov.:
32
show subpopulations
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:
0.000103
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.0000127
AC:
15
AN:
1177646
Hom.:
0
Cov.:
32
AF XY:
0.00000882
AC XY:
5
AN XY:
566924
show subpopulations
Gnomad4 AFR exome
AF:
0.0000427
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000123
Gnomad4 OTH exome
AF:
0.0000415
GnomAD4 genome
AF:
0.0000461
AC:
7
AN:
151994
Hom.:
0
Cov.:
32
AF XY:
0.0000269
AC XY:
2
AN XY:
74262
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000103
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000567

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsSep 25, 2024The c.194T>C (p.I65T) alteration is located in exon 2 (coding exon 2) of the FAM229A gene. This alteration results from a T to C substitution at nucleotide position 194, causing the isoleucine (I) at amino acid position 65 to be replaced by a threonine (T). 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
Pathogenic
0.82
BayesDel_addAF
Pathogenic
0.21
D
BayesDel_noAF
Uncertain
0.070
CADD
Uncertain
26
DANN
Benign
0.93
DEOGEN2
Benign
0.087
T;.
FATHMM_MKL
Benign
0.67
D
LIST_S2
Benign
0.57
T;T
M_CAP
Pathogenic
0.33
D
MetaRNN
Uncertain
0.60
D;D
MutationAssessor
Benign
0.69
N;.
PrimateAI
Pathogenic
0.91
D
PROVEAN
Uncertain
-4.0
D;D
Sift
Uncertain
0.0030
D;.
Sift4G
Benign
0.33
T;D
Vest4
0.51
MVP
0.34
GERP RS
3.6
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.49
gMVP
0.13

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs993568804; hg19: chr1-32827418; API