NM_001167676.2:c.290G>T

Variant names:

• chr1-32361527-C-A
• rs952653339
• NM_001167676.2:c.290G>T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001167676.2(FAM229A):​c.290G>T​(p.Arg97Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R97H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: FAM229A NM_001167676.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.21
• Publications: 0 publications found

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]

LOC124903933 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.833

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.290G>T	p.Arg97Leu	missense	Exon 3 of 3	NP_001161148.1	H3BQW9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM229A	ENST00000432622.2	TSL:2 MANE Select	c.290G>T	p.Arg97Leu	missense	Exon 3 of 3	ENSP00000455971.1	H3BQW9
	FAM229A	ENST00000416512.1	TSL:1	n.2503G>T		non_coding_transcript_exon	Exon 2 of 2
	FAM229A	ENST00000428500.1	TSL:2	c.133G>T	p.Val45Phe	missense	Exon 2 of 2	ENSP00000454338.1	H3BMD6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1203474 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 583056

African (AFR) AF: 0.00 AC: 0 AN: 23756

American (AMR) AF: 0.00 AC: 0 AN: 11448

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17968

East Asian (EAS) AF: 0.00 AC: 0 AN: 27068

South Asian (SAS) AF: 0.00 AC: 0 AN: 54170

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 29918

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4956

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 985104

Other (OTH) AF: 0.00 AC: 0 AN: 49086

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.62
BayesDel_addAF	Pathogenic	0.21	D
BayesDel_noAF	Uncertain	0.060
CADD	Pathogenic	28
DANN	Benign	0.95
DEOGEN2	Benign	0.11	T
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Uncertain	0.86	D
M_CAP	Pathogenic	0.71	D
MetaRNN	Pathogenic	0.83	D
MutationAssessor	Benign	0.69	N
PhyloP100		3.2
PrimateAI	Pathogenic	0.88	D
PROVEAN	Pathogenic	-6.8	D
Sift	Uncertain	0.0030	D
Sift4G	Pathogenic	0.0	D
Vest4		0.57
MVP		0.74
GERP RS		4.2
PromoterAI		-0.0060	Neutral
Varity_R		0.60
gMVP		0.31
Mutation Taster		=82/18	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs952653339; hg19: chr1-32827128;