rs368929102

Variant names:

• chr4-56811703-G-A
• rs368929102
• NM_001271718.2:c.341C>T

Your query was ambiguous. Multiple possible variants found:

• chr4-56811703-G-A
• chr4-56811703-G-C

Variant summary

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

The NM_001271718.2(SPINK2):​c.341C>T​(p.Thr114Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000343 in 1,455,970 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/15 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: SPINK2 NM_001271718.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0670
• Publications: 3 publications found

Genes affected

SPINK2 (HGNC:11245): (serine peptidase inhibitor Kazal type 2) This gene encodes a member of the family of serine protease inhibitors of the Kazal type (SPINK). The encoded protein acts as a trypsin and acrosin inhibitor in the genital tract and is localized in the spermatozoa. The protein has been associated with the progression of lymphomas. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2012]

SPINK2 Gene-Disease associations (from GenCC):

• spermatogenic failure 29

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

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=0.14626282).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001271718.2. 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
	SPINK2	NM_001271718.2	MANE Select	c.341C>T	p.Thr114Ile	missense	Exon 3 of 4	NP_001258647.1	D6RI10
	SPINK2	NM_001271720.2		c.296C>T	p.Thr99Ile	missense	Exon 3 of 4	NP_001258649.1	D6RC51
	SPINK2	NM_001271719.2		c.301C>T	p.Leu101Phe	missense	Exon 3 of 4	NP_001258648.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPINK2	ENST00000506738.6	TSL:2 MANE Select	c.341C>T	p.Thr114Ile	missense	Exon 3 of 4	ENSP00000425961.1	D6RI10
	SPINK2	ENST00000248701.8	TSL:1	c.191C>T	p.Thr64Ile	missense	Exon 3 of 4	ENSP00000248701.4	P20155
	SPINK2	ENST00000504762.1	TSL:2	c.296C>T	p.Thr99Ile	missense	Exon 3 of 4	ENSP00000423858.1	D6RC51

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000343 AC: 5 AN: 1455970 Hom.: 0 Cov.: 29 AF XY: 0.00000414 AC XY: 3 AN XY: 724446

African (AFR) AF: 0.00 AC: 0 AN: 33274

American (AMR) AF: 0.00 AC: 0 AN: 44524

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25952

East Asian (EAS) AF: 0.00 AC: 0 AN: 39522

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86068

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52878

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5730

European-Non Finnish (NFE) AF: 0.00000271 AC: 3 AN: 1108004

Other (OTH) AF: 0.00 AC: 0 AN: 60018

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

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	0.17
BayesDel_addAF	Benign	-0.045	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	15
DANN	Uncertain	1.0
Eigen	Benign	0.052
Eigen_PC	Benign	-0.0051
FATHMM_MKL	Benign	0.069	N
LIST_S2	Benign	0.29	T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.15	T
PhyloP100		-0.067
Vest4		0.16
MVP		0.32
ClinPred		0.81	D
GERP RS		4.5
Varity_R		0.086
Mutation Taster		=75/25	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs368929102; hg19: chr4-57677869;