1-32361759-C-G

Variant names:

• chr1-32361759-C-G
• NM_001167676.2:c.252G>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001167676.2(FAM229A):​c.252G>C​(p.Glu84Asp) 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 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: not found (cov: 33)
• Consequence: FAM229A NM_001167676.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.91

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.25524652).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM229A	NM_001167676.2	c.252G>C	p.Glu84Asp	missense_variant	Exon 2 of 3	ENST00000432622.2	NP_001161148.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM229A	ENST00000432622.2	c.252G>C	p.Glu84Asp	missense_variant	Exon 2 of 3	2	NM_001167676.2	ENSP00000455971.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 27, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.252G>C (p.E84D) alteration is located in exon 2 (coding exon 2) of the FAM229A gene. This alteration results from a G to C substitution at nucleotide position 252, causing the glutamic acid (E) at amino acid position 84 to be replaced by an aspartic acid (D). 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	0.12
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	22
DANN	Benign	0.90
DEOGEN2	Benign	0.078	T;.
FATHMM_MKL	Benign	0.72	D
LIST_S2	Benign	0.57	T;T
M_CAP	Uncertain	0.27	D
MetaRNN	Benign	0.26	T;T
MutationAssessor	Benign	0.69	N;.
PrimateAI	Pathogenic	0.86	D
PROVEAN	Benign	-1.8	N;D
Sift	Benign	0.092	T;.
Sift4G	Benign	0.24	T;D
Vest4		0.21
MVP		0.23
GERP RS		3.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.24
gMVP		0.081

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-32827360;