7-44001173-C-A

Variant names:

• chr7-44001173-C-A
• NM_001378423.2:c.268C>A

Variant summary

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

The NM_001378423.2(SPDYE1):​c.268C>A​(p.Pro90Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000277 in 1,446,296 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 28)
  • Exomes 𝑓: 0.0000028 (0 hom.)
• Consequence: SPDYE1 NM_001378423.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.636

Genes affected

SPDYE1 (HGNC:16408): (speedy/RINGO cell cycle regulator family member E1) This gene is located at chromosome 7p13 which is close to the Williams Beuren syndrome chromosome region 7q11.23. [provided by RefSeq, Jul 2008]

POLR2J4 (HGNC:56874):

ENSG00000273432 (HGNC:):

POLR2J4 (HGNC:28195): (RNA polymerase II subunit J4 (pseudogene))

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=0.2001343).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPDYE1	NM_001378423.2	c.268C>A	p.Pro90Thr	missense_variant	Exon 3 of 9	ENST00000693451.1	NP_001365352.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPDYE1	ENST00000693451.1	c.268C>A	p.Pro90Thr	missense_variant	Exon 3 of 9		NM_001378423.2	ENSP00000509569.1

Frequencies

GnomAD3 genomes Cov.: 28

GnomAD4 exome AF: 0.00000277 AC: 4 AN: 1446296 Hom.: 0 Cov.: 34 AF XY: 0.00000278 AC XY: 2 AN XY: 719870

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.000115

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 28

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jun 07, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.148C>A (p.P50T) alteration is located in exon 1 (coding exon 1) of the SPDYE1 gene. This alteration results from a C to A substitution at nucleotide position 148, causing the proline (P) at amino acid position 50 to be replaced by a threonine (T). 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	0.091
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	14
DANN	Uncertain	0.99
DEOGEN2	Benign	0.069	T
Eigen	Benign	-0.18
Eigen_PC	Benign	-0.47
FATHMM_MKL	Benign	0.026	N
LIST_S2	Benign	0.64	T
M_CAP	Benign	0.0021	T
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Uncertain	2.2	M
PrimateAI	Uncertain	0.53	T
PROVEAN	Uncertain	-2.8	D
REVEL	Benign	0.11
Sift	Uncertain	0.0020	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.043
MutPred		0.26		Loss of glycosylation at P50 (P = 0.0304);
MVP		0.11
MPC		2.6
ClinPred		0.92	D
Varity_R		0.18
gMVP		0.028

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: chr7-44040772;