5-148335651-C-T

Variant names:

• chr5-148335651-C-T
• NM_001040433.2:c.38C>T

Variant summary

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

The NM_001040433.2(SPINK9):​c.38C>T​(p.Thr13Ile) 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 Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SPINK9 NM_001040433.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0920
• Publications: 0 publications found

Genes affected

SPINK9 (HGNC:32951): (serine peptidase inhibitor Kazal type 9) The protein encoded by this gene is a Kazal-type serine protease inhibitor that appears to specifically target kallikrein-related peptidase 5 (KLK5) in the palmo-plantar epidermis. KLK5 is an important initiator of skin desquamation, so the encoded protease inhibitor may regulate skin differentiation in the palms of hands and soles of feet. This cationic protein has also been shown to promote keratinocyte migration by activation of the epidermal growth factor receptor (EGFR). [provided by RefSeq, Dec 2015]

FBXO38-DT (HGNC:55589): (FBXO38 divergent transcript)

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=0.077097535).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001040433.2. 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
	SPINK9	NM_001040433.2	MANE Select	c.38C>T	p.Thr13Ile	missense	Exon 1 of 4	NP_001035523.1	Q5DT21
	FBXO38-DT	NR_105057.1		n.497-27486G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPINK9	ENST00000377906.2	TSL:1 MANE Select	c.38C>T	p.Thr13Ile	missense	Exon 1 of 4	ENSP00000367139.1	Q5DT21
	SPINK9	ENST00000511717.6	TSL:5	c.119-771C>T		intron	N/A	ENSP00000427240.2	D6RJC5
	FBXO38-DT	ENST00000501695.4	TSL:2	n.515-27486G>A		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

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	0.14
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	11
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0096	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.0098	N
LIST_S2	Benign	0.41	T
M_CAP	Benign	0.0030	T
MetaRNN	Benign	0.077	T
MetaSVM	Benign	-1.0	T
PhyloP100		-0.092
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-0.86	N
REVEL	Benign	0.026
Sift	Uncertain	0.021	D
Sift4G	Benign	0.062	T
Polyphen		0.0040	B
Vest4		0.30
MutPred		0.41		Loss of catalytic residue at T13 (P = 0.2427)
MVP		0.088
MPC		0.073
ClinPred		0.15	T
GERP RS		0.53
PromoterAI		-0.010	Neutral
Varity_R		0.042
gMVP		0.29
Mutation Taster		=99/1	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

hg19: chr5-147715214;