chr13-49927986-A-G

Position:

• chr13-49927986-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_020456.4(SPRYD7):​c.323T>C​(p.Leu108Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: SPRYD7 NM_020456.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.29

Genes affected

SPRYD7 (HGNC:14297): (SPRY domain containing 7)

SPRYD7 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.808

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPRYD7	NM_020456.4	c.323T>C	p.Leu108Pro	missense_variant	3/5	ENST00000361840.8	NP_065189.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPRYD7	ENST00000361840.8	c.323T>C	p.Leu108Pro	missense_variant	3/5	1	NM_020456.4	ENSP00000354774.3
SPRYD7	ENST00000378195.6	c.206T>C	p.Leu69Pro	missense_variant	2/4	2		ENSP00000367437.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

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

Mar 04, 2024

The c.323T>C (p.L108P) alteration is located in exon 3 (coding exon 3) of the SPRYD7 gene. This alteration results from a T to C substitution at nucleotide position 323, causing the leucine (L) at amino acid position 108 to be replaced by a proline (P). 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	Pathogenic	0.98
BayesDel_addAF	Pathogenic	0.29	D
BayesDel_noAF	Pathogenic	0.18
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.25	T;.;.
Eigen	Uncertain	0.55
Eigen_PC	Uncertain	0.62
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.78	T;T;.
M_CAP	Benign	0.075	D
MetaRNN	Pathogenic	0.81	D;D;D
MetaSVM	Benign	-0.57	T
MutationAssessor	Benign	1.4	L;.;.
PrimateAI	Uncertain	0.72	T
PROVEAN	Uncertain	-3.9	D;D;.
REVEL	Uncertain	0.56
Sift	Uncertain	0.0070	D;D;.
Sift4G	Uncertain	0.010	D;D;D
Polyphen		0.82	P;P;P
Vest4		0.92
MutPred		0.44		Loss of sheet (P = 0.0054);.;.;
MVP		0.74
MPC		1.6
ClinPred		0.99	D
GERP RS		5.3
Varity_R		0.95
gMVP		0.89

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr13-50502122; COSMIC: COSV62523775; COSMIC: COSV62523775;