Genetic Variant FAM229A:p.Ala75Thr (chr1-32361788-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001167676.2(FAM229A):c.223G>A(p.Ala75Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000121 in 1,322,274 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 10/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000085 ( 0 hom. )

Consequence

FAM229A
NM_001167676.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.976

Publications

0 publications found

Variant links:

Genes affected

FAM229A (HGNC:44652): (family with sequence similarity 229 member A)

FAM229A links:

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]

TSSK3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.18416947).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001167676.2. 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
	FAM229A	NM_001167676.2	MANE Select	c.223G>A	p.Ala75Thr	missense	Exon 2 of 3	NP_001161148.1	H3BQW9

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FAM229A	ENST00000432622.2	TSL:2 MANE Select	c.223G>A	p.Ala75Thr	missense	Exon 2 of 3	ENSP00000455971.1	H3BQW9
FAM229A	ENST00000416512.1	TSL:1	n.2436G>A		non_coding_transcript_exon	Exon 1 of 2
FAM229A	ENST00000428500.1	TSL:2	c.37G>A	p.Ala13Thr	missense	Exon 1 of 2	ENSP00000454338.1	H3BMD6

Frequencies

GnomAD3 genomes

AF:

0.0000394

AC:

AN:

152104

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000855

AC:

AN:

1170062

Hom.:

Cov.:

AF XY:

0.0000107

AC XY:

AN XY:

562254

show subpopulations

African (AFR)

AF:

0.000171

AC:

AN:

23392

American (AMR)

AF:

0.00

AC:

AN:

8836

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

16032

East Asian (EAS)

AF:

0.00

AC:

AN:

26834

South Asian (SAS)

AF:

0.0000903

AC:

AN:

44308

European-Finnish (FIN)

AF:

0.00

AC:

AN:

27730

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4620

European-Non Finnish (NFE)

AF:

0.00000206

AC:

AN:

970396

Other (OTH)

AF:

0.00

AC:

AN:

47914

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000394

AC:

AN:

152212

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74432

show subpopulations

African (AFR)

AF:

0.000144

AC:

AN:

41546

American (AMR)

AF:

0.00

AC:

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5162

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67956

Other (OTH)

AF:

0.00

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000680

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.074

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.48

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.064

FATHMM_MKL

Benign

0.67

LIST_S2

Benign

0.55

M_CAP

Uncertain

0.10

MetaRNN

Benign

0.18

MutationAssessor

Benign

0.55

PhyloP100

0.98

PrimateAI

Uncertain

0.79

PROVEAN

Benign

-1.9

Sift

Benign

0.26

Sift4G

Benign

0.67

Vest4

0.11

MVP

0.26

GERP RS

1.6

PromoterAI

0.035

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.062

gMVP

0.12

Mutation Taster

=96/4

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over