19-372677-G-C

Position:

• chr19-372677-G-C

Variant summary

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

The NM_016585.5(SPMAP2):​c.589C>G​(p.Leu197Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 35)
• Consequence: SPMAP2 NM_016585.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.29

Genes affected

SPMAP2 (HGNC:13706): (sperm microtubule associated protein 2) This gene is specifically expressed in the nucleus of haploid male germ cells. The orthologous gene in mice encodes a protein that may play a role in protein assembly through interactions with T-complex protein 1 subunit epsilon. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Nov 2011]

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
SPMAP2	NM_016585.5	c.589C>G	p.Leu197Val	missense_variant	5/8	ENST00000342640.9	NP_057669.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
THEG	ENST00000342640.9	c.589C>G	p.Leu197Val	missense_variant	5/8	1	NM_016585.5	ENSP00000340088.3
THEG	ENST00000346878.3	c.517C>G	p.Leu173Val	missense_variant	4/7	2		ENSP00000264820.3
THEG	ENST00000530711.3	c.86+1622C>G		intron_variant		3		ENSP00000475782.2
THEG	ENST00000528213.1	n.396C>G		non_coding_transcript_exon_variant	3/5	5

Frequencies

GnomAD3 genomes Cov.: 35

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 35

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

Oct 20, 2021

The c.589C>G (p.L197V) alteration is located in exon 5 (coding exon 5) of the THEG gene. This alteration results from a C to G substitution at nucleotide position 589, causing the leucine (L) at amino acid position 197 to be replaced by a valine (V). 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	0.52
BayesDel_addAF	Benign	-0.032	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.37	.;T
Eigen	Uncertain	0.43
Eigen_PC	Uncertain	0.29
FATHMM_MKL	Benign	0.68	D
LIST_S2	Benign	0.78	T;T
M_CAP	Benign	0.0097	T
MetaRNN	Uncertain	0.54	D;D
MetaSVM	Benign	-0.77	T
MutationAssessor	Benign	1.9	.;L
PrimateAI	Uncertain	0.50	T
PROVEAN	Uncertain	-2.6	D;D
REVEL	Benign	0.15
Sift	Pathogenic	0.0	D;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		1.0	D;D
Vest4		0.71
MutPred		0.35		.;Loss of helix (P = 0.028);
MVP		0.33
MPC		0.32
ClinPred		0.97	D
GERP RS		3.3
Varity_R		0.95
gMVP		0.19

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr19-372677;