chr4-176192972-T-A

Variant names:

• chr4-176192972-T-A
• NM_144644.4:c.453A>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_144644.4(SPATA4):​c.453A>T​(p.Leu151Phe) 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. 14/22 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: SPATA4 NM_144644.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.108
• Publications: 0 publications found

Genes affected

SPATA4 (HGNC:17333): (spermatogenesis associated 4) Predicted to enable microtubule binding activity. Predicted to be involved in regulation of cytoskeleton organization. Predicted to be located in cytoplasm. Predicted to be active in axoneme. [provided by Alliance of Genome Resources, Apr 2022]

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=0.25072128).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_144644.4. 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
	SPATA4	NM_144644.4	MANE Select	c.453A>T	p.Leu151Phe	missense	Exon 3 of 6	NP_653245.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPATA4	ENST00000280191.7	TSL:1 MANE Select	c.453A>T	p.Leu151Phe	missense	Exon 3 of 6	ENSP00000280191.2	Q8NEY3
	SPATA4	ENST00000515234.1	TSL:1	c.-67A>T		5_prime_UTR	Exon 2 of 5	ENSP00000422290.1	G5E9Y6
	SPATA4	ENST00000508699.1	TSL:3	n.*172A>T		splice_region non_coding_transcript_exon	Exon 3 of 3	ENSP00000425950.1	H0YA30

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

EpiCase AF: 0.0000545

EpiControl AF: 0.00

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	0.17
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0061	T
Eigen	Benign	-0.35
Eigen_PC	Benign	-0.44
FATHMM_MKL	Benign	0.25	N
LIST_S2	Benign	0.75	T
M_CAP	Benign	0.0094	T
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	L
PhyloP100		-0.11
PrimateAI	Benign	0.45	T
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.15
Sift	Uncertain	0.019	D
Sift4G	Benign	0.24	T
Polyphen		0.99	D
Vest4		0.34
MutPred		0.53		Loss of stability (P = 0.0478)
MVP		0.12
MPC		0.36
ClinPred		0.78	D
GERP RS		-1.6
Varity_R		0.17
gMVP		0.44
Mutation Taster		=82/18	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: chr4-177114123;