13-49921504-C-T

Position:

• chr13-49921504-C-T

Variant summary

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

The NM_020456.4(SPRYD7):​c.467G>A​(p.Arg156Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000685 in 1,460,474 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000068 (0 hom.)
• Consequence: SPRYD7 NM_020456.4 missense
• 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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPRYD7	NM_020456.4	c.467G>A	p.Arg156Gln	missense_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.467G>A	p.Arg156Gln	missense_variant	4/5	1	NM_020456.4	ENSP00000354774.3
SPRYD7	ENST00000378195.6	c.350G>A	p.Arg117Gln	missense_variant	3/4	2		ENSP00000367437.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251266 Hom.: 0 AF XY: 0.00000736 AC XY: 1 AN XY: 135818

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000685 AC: 10 AN: 1460474 Hom.: 0 Cov.: 29 AF XY: 0.00000826 AC XY: 6 AN XY: 726632

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: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000810

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

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 23, 2023

The c.467G>A (p.R156Q) alteration is located in exon 4 (coding exon 4) of the SPRYD7 gene. This alteration results from a G to A substitution at nucleotide position 467, causing the arginine (R) at amino acid position 156 to be replaced by a glutamine (Q). 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	0.75
BayesDel_addAF	Uncertain	0.068	T
BayesDel_noAF	Uncertain	0.030
CADD	Pathogenic	31
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.26	T;.;.
Eigen	Pathogenic	0.68
Eigen_PC	Pathogenic	0.70
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Pathogenic	0.99	D;D;.
M_CAP	Benign	0.049	D
MetaRNN	Uncertain	0.74	D;D;D
MetaSVM	Benign	-0.30	T
MutationAssessor	Benign	1.8	L;.;.
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	-2.3	N;N;.
REVEL	Benign	0.27
Sift	Uncertain	0.0070	D;D;.
Sift4G	Uncertain	0.015	D;D;D
Polyphen		0.98	D;P;P
Vest4		0.88
MutPred		0.66		Loss of methylation at R156 (P = 0.072);.;.;
MVP		0.83
MPC		0.98
ClinPred		0.92	D
GERP RS		5.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.74
gMVP		0.56

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs754283290; hg19: chr13-50495640; COSMIC: COSV62524460;