14-64787102-G-C

Variant names:

• chr14-64787102-G-C
• NM_001355436.2:c.2863C>G

Variant summary

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

The NM_001355436.2(SPTB):​c.2863C>G​(p.Arg955Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,457,162 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: SPTB NM_001355436.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.754

Genes affected

SPTB (HGNC:11274): (spectrin beta, erythrocytic) This locus encodes a member of the spectrin gene family. Spectrin proteins, along with ankyrin, play a role in cell membrane organization and stability. The protein encoded by this locus functions in stability of erythrocyte membranes, and mutations in this gene have been associated with spherocytosis type 2, hereditary elliptocytosis, and neonatal hemolytic anemia. Alternatively spliced transcript variants have been described. [provided by RefSeq, Nov 2009]

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=0.14211649).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPTB	NM_001355436.2	c.2863C>G	p.Arg955Gly	missense_variant	Exon 16 of 36	ENST00000644917.1	NP_001342365.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPTB	ENST00000644917.1	c.2863C>G	p.Arg955Gly	missense_variant	Exon 16 of 36		NM_001355436.2	ENSP00000495909.1
SPTB	ENST00000389722.7	c.2863C>G	p.Arg955Gly	missense_variant	Exon 15 of 35	2		ENSP00000374372.3
SPTB	ENST00000389720.4	c.2863C>G	p.Arg955Gly	missense_variant	Exon 16 of 32	5		ENSP00000374370.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1457162 Hom.: 0 Cov.: 35 AF XY: 0.00 AC XY: 0 AN XY: 725200

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000224

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.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.096	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	18
DANN	Benign	0.64
DEOGEN2	Benign	0.33	.;.;.;T;T
Eigen	Benign	-0.82
Eigen_PC	Benign	-0.66
FATHMM_MKL	Benign	0.28	N
LIST_S2	Benign	0.85	.;.;D;.;D
M_CAP	Benign	0.029	D
MetaRNN	Benign	0.14	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.3	L;L;L;L;L
PrimateAI	Benign	0.45	T
PROVEAN	Benign	2.2	N;.;N;N;N
REVEL	Benign	0.14
Sift	Benign	0.69	T;.;T;T;T
Sift4G	Benign	0.65	T;.;T;T;T
Polyphen		0.0	.;.;.;B;B
Vest4		0.17
MutPred		0.60		Gain of catalytic residue at V956 (P = 0.0223);Gain of catalytic residue at V956 (P = 0.0223);Gain of catalytic residue at V956 (P = 0.0223);Gain of catalytic residue at V956 (P = 0.0223);Gain of catalytic residue at V956 (P = 0.0223);
MVP		0.15
MPC		0.25
ClinPred		0.27	T
GERP RS		3.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Varity_R		0.21
gMVP		0.21

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: chr14-65253820;