NM_016585.5:c.1023G>C

Variant names:

• chr19-362317-C-G
• rs756805620
• NM_016585.5:c.1023G>C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_016585.5(SPMAP2):​c.1023G>C​(p.Lys341Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000211 in 1,609,980 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 30)
  • Exomes 𝑓: 0.000021 (0 hom.)
• Consequence: SPMAP2 NM_016585.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.00300
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.040730596).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016585.5. 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
	SPMAP2	NM_016585.5	MANE Select	c.1023G>C	p.Lys341Asn	missense	Exon 8 of 8	NP_057669.1	Q9P2T0-1
	SPMAP2	NM_199202.3		c.951G>C	p.Lys317Asn	missense	Exon 7 of 7	NP_954672.1	Q9P2T0-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPMAP2	ENST00000342640.9	TSL:1 MANE Select	c.1023G>C	p.Lys341Asn	missense	Exon 8 of 8	ENSP00000340088.3	Q9P2T0-1
	SPMAP2	ENST00000346878.3	TSL:2	c.951G>C	p.Lys317Asn	missense	Exon 7 of 7	ENSP00000264820.3	Q9P2T0-2
	SPMAP2	ENST00000530711.3	TSL:3	c.356G>C	p.Ser119Thr	missense	Exon 3 of 3	ENSP00000475782.2	U3KQD4

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152170 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000845 AC: 21 AN: 248538 AF XY: 0.0000969

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00115

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000213 AC: 31 AN: 1457810 Hom.: 0 Cov.: 31 AF XY: 0.0000193 AC XY: 14 AN XY: 724832

African (AFR) AF: 0.00 AC: 0 AN: 33452

American (AMR) AF: 0.00 AC: 0 AN: 44258

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26106

East Asian (EAS) AF: 0.000505 AC: 20 AN: 39614

South Asian (SAS) AF: 0.00 AC: 0 AN: 84818

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5756

European-Non Finnish (NFE) AF: 0.00000901 AC: 10 AN: 1110114

Other (OTH) AF: 0.0000166 AC: 1 AN: 60278

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152170 Hom.: 0 Cov.: 30 AF XY: 0.0000269 AC XY: 2 AN XY: 74338

African (AFR) AF: 0.00 AC: 0 AN: 41432

American (AMR) AF: 0.00 AC: 0 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000385 AC: 2 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68036

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000340

ExAC AF: 0.0000412 AC: 5

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	Uncertain	0.45
BayesDel_addAF	Benign	-0.45	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	15
DANN	Benign	0.97
DEOGEN2	Benign	0.25	T
Eigen	Benign	-0.54
Eigen_PC	Benign	-0.67
FATHMM_MKL	Benign	0.34	N
LIST_S2	Benign	0.65	T
M_CAP	Benign	0.0042	T
MetaRNN	Benign	0.041	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		0.0030
PrimateAI	Benign	0.36	T
PROVEAN	Uncertain	-2.5	N
REVEL	Benign	0.040
Sift	Uncertain	0.029	D
Sift4G	Uncertain	0.020	D
Polyphen		0.081	B
Vest4		0.18
MutPred		0.21		Loss of methylation at K341 (P = 0.0496)
MVP		0.048
MPC		0.17
ClinPred		0.11	T
GERP RS		-0.66
Varity_R		0.23
gMVP		0.23
Mutation Taster		=89/11	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: rs756805620; hg19: chr19-362317;