13-49921579-C-A

Position:

• chr13-49921579-C-A

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_020456.4(SPRYD7):​c.392G>T​(p.Gly131Val) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000209 in 1,433,546 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: SPRYD7 NM_020456.4 missense, splice_region
• Scores: Splicing: ADA: 0.9687
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.68

Genes affected

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

SPRYD7 (HGNC:):

ACMG classification

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.968

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPRYD7	NM_020456.4	c.392G>T	p.Gly131Val	missense_variant, splice_region_variant	4/5	ENST00000361840.8	NP_065189.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPRYD7	ENST00000361840.8	c.392G>T	p.Gly131Val	missense_variant, splice_region_variant	4/5	1	NM_020456.4	ENSP00000354774.3
SPRYD7	ENST00000378195.6	c.275G>T	p.Gly92Val	missense_variant, splice_region_variant	3/4	2		ENSP00000367437.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000209 AC: 3 AN: 1433546 Hom.: 0 Cov.: 24 AF XY: 0.00 AC XY: 0 AN XY: 714804

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000276

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

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

May 31, 2023

The c.392G>T (p.G131V) alteration is located in exon 4 (coding exon 4) of the SPRYD7 gene. This alteration results from a G to T substitution at nucleotide position 392, causing the glycine (G) at amino acid position 131 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	Pathogenic	0.98
BayesDel_addAF	Pathogenic	0.42	D
BayesDel_noAF	Pathogenic	0.36
CADD	Pathogenic	30
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.50	T;.;.
Eigen	Pathogenic	0.71
Eigen_PC	Pathogenic	0.69
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.95	D;D;.
M_CAP	Uncertain	0.23	D
MetaRNN	Pathogenic	0.97	D;D;D
MetaSVM	Uncertain	0.59	D
MutationAssessor	Uncertain	2.2	M;.;.
PrimateAI	Pathogenic	0.89	D
PROVEAN	Pathogenic	-8.1	D;D;.
REVEL	Pathogenic	0.88
Sift	Uncertain	0.0030	D;D;.
Sift4G	Uncertain	0.0030	D;D;D
Polyphen		0.96	D;P;P
Vest4		0.97
MutPred		0.82		Gain of sheet (P = 0.0827);.;.;
MVP		0.85
MPC		1.6
ClinPred		1.0	D
GERP RS		5.4
Varity_R		0.97
gMVP		0.88

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Pathogenic	0.97
dbscSNV1_RF	Pathogenic	0.90
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: chr13-50495715;