1-16399422-G-A

Position:

• chr1-16399422-G-A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_198546.1(SPATA21):​c.1274C>T​(p.Ala425Val) 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SPATA21 NM_198546.1 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.08

Genes affected

SPATA21 (HGNC:28026): (spermatogenesis associated 21) Predicted to enable calcium ion binding activity. [provided by Alliance of Genome Resources, Apr 2022]

SPATA21 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0179542).
• BP6: Variant 1-16399422-G-A is Benign according to our data. Variant chr1-16399422-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3168270.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPATA21	NM_198546.1	c.1274C>T	p.Ala425Val	missense_variant	12/13	ENST00000335496.5	NP_940948.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPATA21	ENST00000335496.5	c.1274C>T	p.Ala425Val	missense_variant	12/13	1	NM_198546.1	ENSP00000335612.1
SPATA21	ENST00000540400.1	c.1205C>T	p.Ala402Val	missense_variant	10/11	1		ENSP00000440046.1
SPATA21	ENST00000491418.5	c.398C>T	p.Ala133Val	missense_variant	4/5	5		ENSP00000420753.1
SPATA21	ENST00000466212.5	n.2720C>T		non_coding_transcript_exon_variant	15/17	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 03, 2024

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.063
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	0.55
DANN	Benign	0.64
DEOGEN2	Benign	0.000069	.;T;.
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.0044	N
LIST_S2	Benign	0.50	T;T;T
M_CAP	Benign	0.0041	T
MetaRNN	Benign	0.018	T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	-1.8	.;N;.
PrimateAI	Benign	0.24	T
PROVEAN	Benign	1.2	N;N;N
REVEL	Benign	0.14
Sift	Benign	1.0	T;T;T
Sift4G	Benign	1.0	T;T;T
Polyphen		0.0	.;B;.
Vest4		0.094, 0.095
MutPred		0.15		.;Gain of sheet (P = 0.0827);.;
MVP		0.048
MPC		0.089
ClinPred		0.037	T
GERP RS		2.6
Varity_R		0.023
gMVP		0.066

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: chr1-16725917;