chr1-32362058-C-T

Position:

• chr1-32362058-C-T

Variant summary

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

The NM_001167676.2(FAM229A):​c.34G>A​(p.Ala12Thr) 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)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: FAM229A NM_001167676.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.367

Genes affected

FAM229A (HGNC:44652): (family with sequence similarity 229 member A)

FAM229A (HGNC:):

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=0.13542786).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FAM229A	NM_001167676.2	c.34G>A	p.Ala12Thr	missense_variant	1/3	ENST00000432622.2	NP_001161148.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FAM229A	ENST00000432622.2	c.34G>A	p.Ala12Thr	missense_variant	1/3	2	NM_001167676.2	ENSP00000455971.1
FAM229A	ENST00000416512.1	n.2166G>A		non_coding_transcript_exon_variant	1/2	1
TSSK3	ENST00000574315.1	c.-80-1537C>T		intron_variant		3		ENSP00000459187.1
FAM229A	ENST00000415596.1	n.205-7G>A		splice_region_variant, intron_variant		3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1289988 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 632612

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 10, 2023

The c.34G>A (p.A12T) alteration is located in exon 1 (coding exon 1) of the FAM229A gene. This alteration results from a G to A substitution at nucleotide position 34, causing the alanine (A) at amino acid position 12 to be replaced by a threonine (T). 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	0.071
BayesDel_addAF	Benign	-0.087	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0024	T
FATHMM_MKL	Benign	0.36	N
LIST_S2	Benign	0.46	T
M_CAP	Uncertain	0.18	D
MetaRNN	Benign	0.14	T
MutationAssessor	Benign	0.69	N
MutationTaster	Benign	0.73	N
PrimateAI	Pathogenic	0.81	D
PROVEAN	Benign	-1.2	N
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Vest4		0.074
MVP		0.19
GERP RS		3.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Varity_R		0.26
gMVP		0.12

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: chr1-32827659;