NM_001167676.2:c.139C>T

Variant names:

• chr1-32361872-G-A
• rs1641708397
• NM_001167676.2:c.139C>T

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.139C>T​(p.Pro47Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000168 in 1,188,348 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: not found (cov: 33)
  • Exomes 𝑓: 0.0000017 (0 hom.)
• Consequence: FAM229A NM_001167676.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.217
• 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=0.14514238).

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.139C>T	p.Pro47Ser	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.139C>T	p.Pro47Ser	missense	Exon 2 of 3	ENSP00000455971.1	H3BQW9
	FAM229A	ENST00000416512.1	TSL:1	n.2352C>T		non_coding_transcript_exon	Exon 1 of 2
	TSSK3	ENST00000574315.1	TSL:3	c.-80-1723G>A		intron	N/A	ENSP00000459187.1	I3L1X4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000168 AC: 2 AN: 1188348 Hom.: 0 Cov.: 32 AF XY: 0.00000349 AC XY: 2 AN XY: 572888

African (AFR) AF: 0.00 AC: 0 AN: 23462

American (AMR) AF: 0.00 AC: 0 AN: 9020

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16398

East Asian (EAS) AF: 0.00 AC: 0 AN: 26926

South Asian (SAS) AF: 0.0000204 AC: 1 AN: 49036

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 28506

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4276

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 981900

Other (OTH) AF: 0.0000205 AC: 1 AN: 48824

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	Benign	0.071
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	16
DANN	Benign	0.97
DEOGEN2	Benign	0.066	T
FATHMM_MKL	Benign	0.52	D
LIST_S2	Benign	0.46	T
M_CAP	Uncertain	0.21	D
MetaRNN	Benign	0.15	T
MutationAssessor	Benign	0.55	N
PhyloP100		0.22
PrimateAI	Uncertain	0.78	T
PROVEAN	Uncertain	-3.2	D
Sift	Benign	0.12	T
Sift4G	Pathogenic	0.0	D
Vest4		0.071
MVP		0.41
GERP RS		0.49
PromoterAI		0.0020	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.12
gMVP		0.15
Mutation Taster		=99/1	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: rs1641708397; hg19: chr1-32827473;