16-67827340-G-A

Variant names:

• chr16-67827340-G-A
• rs193921053
• NM_001288990.3:c.1756G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001288990.3(TSNAXIP1):​c.1756G>A​(p.Ala586Thr) 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. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TSNAXIP1 NM_001288990.3 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: -0.342
• Publications: 4 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.03826958).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001288990.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TSNAXIP1	NM_001288990.3	MANE Select	c.1756G>A	p.Ala586Thr	missense	Exon 14 of 16	NP_001275919.1
	TSNAXIP1	NM_018430.4		c.1594G>A	p.Ala532Thr	missense	Exon 14 of 16	NP_060900.2
	TSNAXIP1	NM_001288991.3		c.1549G>A	p.Ala517Thr	missense	Exon 12 of 14	NP_001275920.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TSNAXIP1	ENST00000561639.6	TSL:2 MANE Select	c.1756G>A	p.Ala586Thr	missense	Exon 14 of 16	ENSP00000457241.1
	TSNAXIP1	ENST00000388833.7	TSL:1	c.1594G>A	p.Ala532Thr	missense	Exon 14 of 16	ENSP00000373485.3
	TSNAXIP1	ENST00000466164.5	TSL:1	n.*1316G>A		non_coding_transcript_exon	Exon 10 of 12	ENSP00000458938.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

Prostate cancer Uncertain:1

Science for Life laboratory, Karolinska Institutet

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: literature only

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.068
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	1.1
DANN	Benign	0.75
DEOGEN2	Benign	0.012	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.039	N
LIST_S2	Benign	0.67	T
M_CAP	Benign	0.0018	T
MetaRNN	Benign	0.038	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.60	N
PhyloP100		-0.34
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.81	N
REVEL	Benign	0.023
Sift	Benign	0.28	T
Sift4G	Benign	0.38	T
Polyphen		0.0080	B
Vest4		0.055
MutPred		0.18		Loss of helix (P = 0.028)
MVP		0.014
MPC		0.074
ClinPred		0.067	T
GERP RS		-3.5
Varity_R		0.041
gMVP		0.093

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

dbSNP: rs193921053; hg19: chr16-67861243; COSMIC: COSV54651352; COSMIC: COSV54651352;