16-67820924-G-C

Position:

• chr16-67820924-G-C

Variant summary

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

The NM_001288990.3(TSNAXIP1):​c.233G>C​(p.Cys78Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000275 in 1,452,078 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000028 (0 hom.)
• Consequence: TSNAXIP1 NM_001288990.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.39

Genes affected

TSNAXIP1 (HGNC:18586): (translin associated factor X interacting protein 1) Predicted to be involved in cell differentiation and spermatogenesis. Predicted to be located in perinuclear region of cytoplasm. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

TSNAXIP1 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TSNAXIP1	NM_001288990.3	c.233G>C	p.Cys78Ser	missense_variant	3/16	ENST00000561639.6	NP_001275919.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TSNAXIP1	ENST00000561639.6	c.233G>C	p.Cys78Ser	missense_variant	3/16	2	NM_001288990.3	ENSP00000457241.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000275 AC: 4 AN: 1452078 Hom.: 0 Cov.: 33 AF XY: 0.00000277 AC XY: 2 AN XY: 721840

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: 0.00000271

Gnomad4 OTH exome AF: 0.0000167

GnomAD4 genome Cov.: 32

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

Aug 21, 2023

The c.71G>C (p.C24S) alteration is located in exon 3 (coding exon 1) of the TSNAXIP1 gene. This alteration results from a G to C substitution at nucleotide position 71, causing the cysteine (C) at amino acid position 24 to be replaced by a serine (S). 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	Uncertain	0.39
BayesDel_addAF	Pathogenic	0.40	D
BayesDel_noAF	Pathogenic	0.33
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.028	.;.;T
Eigen	Uncertain	0.67
Eigen_PC	Uncertain	0.65
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.70	T;T;T
M_CAP	Benign	0.013	T
MetaRNN	Uncertain	0.58	D;D;D
MetaSVM	Uncertain	-0.27	T
MutationAssessor	Uncertain	2.2	.;.;M
MutationTaster	Benign	0.99	D;D;D
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-0.99	N;D;N
REVEL	Benign	0.22
Sift	Uncertain	0.0090	D;D;D
Sift4G	Benign	0.25	T;T;T
Polyphen		1.0	D;.;D
Vest4		0.77
MutPred		0.42		Loss of catalytic residue at P77 (P = 0.0154);Loss of catalytic residue at P77 (P = 0.0154);.;
MVP		0.30
MPC		0.48
ClinPred		0.95	D
GERP RS		5.0
Varity_R		0.68
gMVP		0.16

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: chr16-67854827;