NM_001167676.2:c.252G>C

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 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
• 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]

ACMG classification

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=0.25524652).

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.252G>C	p.Glu84Asp	missense	Exon 2 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.252G>C	p.Glu84Asp	missense	Exon 2 of 3	ENSP00000455971.1	H3BQW9
	FAM229A	ENST00000416512.1	TSL:1	n.2465G>C		non_coding_transcript_exon	Exon 1 of 2
	FAM229A	ENST00000428500.1	TSL:2	c.66G>C	p.Glu22Asp	missense	Exon 1 of 2	ENSP00000454338.1	H3BMD6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

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	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
M_CAP	Uncertain	0.27	D
MetaRNN	Benign	0.26	T
MutationAssessor	Benign	0.69	N
PhyloP100		2.9
PrimateAI	Pathogenic	0.86	D
PROVEAN	Benign	-1.8	N
Sift	Benign	0.092	T
Sift4G	Benign	0.24	T
Vest4		0.21
MVP		0.23
GERP RS		3.8
PromoterAI		0.014	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.24
gMVP		0.081
Mutation Taster		=88/12	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

hg19: chr1-32827360;