Variant chr1-158614301-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_003126.4(SPTA1):c.6794T>A(p.Ile2265Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I2265T) has been classified as Benign.

Frequency

Genomes: not found (cov: 30)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

SPTA1
NM_003126.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.96

Variant links:

Genes affected

SPTA1 (HGNC:11272): (spectrin alpha, erythrocytic 1) This gene encodes a member of a family of molecular scaffold proteins that link the plasma membrane to the actin cytoskeleton and functions in the determination of cell shape, arrangement of transmembrane proteins, and organization of organelles. The encoded protein is primarily composed of 22 spectrin repeats which are involved in dimer formation. It forms a component of the erythrocyte plasma membrane. Mutations in this gene result in a variety of hereditary red blood cell disorders, including elliptocytosis-2, pyropoikilocytosis, and spherocytosis, type 3. [provided by RefSeq, Aug 2017]

SPTA1 links:

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ACMG classification

Classification made for transcript

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=0.0779095).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
SPTA1	NM_003126.4 linkuse as main transcript	c.6794T>A	p.Ile2265Asn	missense_variant	49/52	ENST00000643759.2	NP_003117.2
SPTA1	XM_011509916.3 linkuse as main transcript	c.6794T>A	p.Ile2265Asn	missense_variant	50/53		XP_011508218.1
SPTA1	XM_011509917.4 linkuse as main transcript	c.6776T>A	p.Ile2259Asn	missense_variant	48/51		XP_011508219.1
SPTA1	XM_047428883.1 linkuse as main transcript	c.6473T>A	p.Ile2158Asn	missense_variant	49/52		XP_047284839.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPTA1	ENST00000643759.2 linkuse as main transcript	c.6794T>A	p.Ile2265Asn	missense_variant	49/52		NM_003126.4	ENSP00000495214	P1	P02549-1
SPTA1	ENST00000481212.5 linkuse as main transcript	n.235T>A		non_coding_transcript_exon_variant	1/3	3
SPTA1	ENST00000498708.1 linkuse as main transcript	n.226T>A		non_coding_transcript_exon_variant	3/5	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

1429264

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

712372

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.084

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Benign

0.90

DEOGEN2

Benign

0.18

T;T

Eigen

Benign

-0.85

Eigen_PC

Benign

-0.73

FATHMM_MKL

Uncertain

0.80

LIST_S2

Pathogenic

0.99

.;D

M_CAP

Benign

0.027

MetaRNN

Benign

0.078

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.34

N;N

MutationTaster

Benign

1.0

P;P

PrimateAI

Benign

0.35

REVEL

Benign

0.055

Sift4G

Uncertain

0.040

D;.

Polyphen

0.0

B;B

Vest4

0.26

MutPred

0.45

Gain of disorder (P = 0.0251);Gain of disorder (P = 0.0251);

MVP

0.48

MPC

0.039

ClinPred

0.083

GERP RS

1.3

Varity_R

0.065

gMVP

0.25

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over