1-32361527-C-T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001167676.2(FAM229A):​c.290G>A​(p.Arg97His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000216 in 1,203,474 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.000022 (0 hom.)
• Consequence: FAM229A NM_001167676.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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>A	p.Arg97His	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>A	p.Arg97His	missense	Exon 3 of 3	ENSP00000455971.1	H3BQW9
	FAM229A	ENST00000416512.1	TSL:1	n.2503G>A		non_coding_transcript_exon	Exon 2 of 2
	FAM229A	ENST00000428500.1	TSL:2	c.133G>A	p.Val45Ile	missense	Exon 2 of 2	ENSP00000454338.1	H3BMD6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.0000216 AC: 26 AN: 1203474 Hom.: 0 Cov.: 31 AF XY: 0.0000274 AC XY: 16 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: 0.0000244 AC: 24 AN: 985104

Other (OTH) AF: 0.0000407 AC: 2 AN: 49086

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.43
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.010
CADD	Pathogenic	32
DANN	Benign	0.97
DEOGEN2	Benign	0.10	T
FATHMM_MKL	Benign	0.68	D
LIST_S2	Uncertain	0.89	D
M_CAP	Pathogenic	0.69	D
MetaRNN	Uncertain	0.44	T
MutationAssessor	Benign	0.69	N
PhyloP100		3.2
PrimateAI	Pathogenic	0.87	D
PROVEAN	Pathogenic	-4.8	D
Sift	Uncertain	0.0030	D
Sift4G	Pathogenic	0.0	D
Vest4		0.41
MVP		0.47
GERP RS		4.2
PromoterAI		-0.0060	Neutral
Varity_R		0.48
gMVP		0.22
Mutation Taster		=84/16	polymorphism

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

Other links and lift over

dbSNP: rs952653339; hg19: chr1-32827128;