12-49496846-G-C

Variant names:

• chr12-49496846-G-C
• rs765573967
• NM_023071.4:c.540G>C

Variant summary

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

The NM_023071.4(SPATS2):​c.540G>C​(p.Gln180His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,810 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: SPATS2 NM_023071.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.711
• Publications: 0 publications found

Genes affected

SPATS2 (HGNC:18650): (spermatogenesis associated serine rich 2) Enables RNA binding activity. Located in cytosol. [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=0.15416431).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_023071.4. 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
	SPATS2	NM_023071.4	MANE Select	c.540G>C	p.Gln180His	missense	Exon 8 of 14	NP_075559.2	Q86XZ4
	SPATS2	NM_001293285.2		c.540G>C	p.Gln180His	missense	Exon 9 of 15	NP_001280214.1	Q86XZ4
	SPATS2	NM_001293286.2		c.540G>C	p.Gln180His	missense	Exon 7 of 13	NP_001280215.1	Q86XZ4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPATS2	ENST00000552918.6	TSL:2 MANE Select	c.540G>C	p.Gln180His	missense	Exon 8 of 14	ENSP00000447947.2	Q86XZ4
	SPATS2	ENST00000321898.10	TSL:1	c.540G>C	p.Gln180His	missense	Exon 7 of 13	ENSP00000326841.6	Q86XZ4
	SPATS2	ENST00000553127.5	TSL:1	c.540G>C	p.Gln180His	missense	Exon 9 of 15	ENSP00000448228.1	Q86XZ4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251256 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461810 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727200

African (AFR) AF: 0.00 AC: 0 AN: 33476

American (AMR) AF: 0.00 AC: 0 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.0000756 AC: 3 AN: 39690

South Asian (SAS) AF: 0.00 AC: 0 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53414

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111972

Other (OTH) AF: 0.00 AC: 0 AN: 60394

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.00000824 AC: 1

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	0.12
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.019	T
Eigen	Benign	-0.022
Eigen_PC	Benign	0.035
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Benign	0.69	T
M_CAP	Benign	0.0051	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.81	L
PhyloP100		0.71
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.10
Sift	Benign	0.042	D
Sift4G	Benign	0.25	T
Polyphen		0.53	P
Vest4		0.23
MutPred		0.60		Loss of helix (P = 0.0033)
MVP		0.082
MPC		0.43
ClinPred		0.46	T
GERP RS		2.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.059
gMVP		0.34
Mutation Taster		=84/16	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

dbSNP: rs765573967; hg19: chr12-49890629;