13-49915104-G-A

Position:

• chr13-49915104-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_020456.4(SPRYD7):​c.550C>T​(p.Pro184Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000567 in 1,410,708 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 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)
  • Exomes 𝑓: 0.0000057 (0 hom.)
• Consequence: SPRYD7 NM_020456.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.31

Genes affected

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

SPRYD7 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.092966706).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPRYD7	NM_020456.4	c.550C>T	p.Pro184Ser	missense_variant	5/5	ENST00000361840.8	NP_065189.1
SPRYD7	NM_001127482.3	c.433C>T	p.Pro145Ser	missense_variant	4/4		NP_001120954.1
SPRYD7	NR_023351.3	n.371C>T		non_coding_transcript_exon_variant	3/3
SPRYD7	XR_007063693.1	n.3088C>T		non_coding_transcript_exon_variant	6/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPRYD7	ENST00000361840.8	c.550C>T	p.Pro184Ser	missense_variant	5/5	1	NM_020456.4	ENSP00000354774.3
SPRYD7	ENST00000378195.6	c.433C>T	p.Pro145Ser	missense_variant	4/4	2		ENSP00000367437.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000567 AC: 8 AN: 1410708 Hom.: 0 Cov.: 27 AF XY: 0.00000285 AC XY: 2 AN XY: 701530

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: 0.0000258

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000553

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000611 Hom.: 0

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

Jun 22, 2023

The c.550C>T (p.P184S) alteration is located in exon 5 (coding exon 5) of the SPRYD7 gene. This alteration results from a C to T substitution at nucleotide position 550, causing the proline (P) at amino acid position 184 to be replaced by a serine (S). 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	Benign	0.062
BayesDel_addAF	Benign	-0.087	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	21
DANN	Benign	0.93
DEOGEN2	Benign	0.020	T;.;.
Eigen	Benign	-0.25
Eigen_PC	Benign	-0.013
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.96	D;D;.
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.093	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.81	L;.;.
PrimateAI	Benign	0.48	T
PROVEAN	Benign	0.24	N;N;.
REVEL	Benign	0.042
Sift	Benign	0.62	T;T;.
Sift4G	Benign	1.0	T;T;T
Polyphen		0.0	B;B;B
Vest4		0.32
MVP		0.59
MPC		0.54
ClinPred		0.28	T
GERP RS		4.8
Varity_R		0.12
gMVP		0.11

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: chr13-50489240;