14-64786514-T-G

Position:

• chr14-64786514-T-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.3451A>C​(p.Asn1151His) 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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N1151D) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SPTB NM_001355436.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.678

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=0.13078207).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPTB	NM_001355436.2	c.3451A>C	p.Asn1151His	missense_variant	16/36	ENST00000644917.1	NP_001342365.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPTB	ENST00000644917.1	c.3451A>C	p.Asn1151His	missense_variant	16/36		NM_001355436.2	ENSP00000495909	P1
SPTB	ENST00000389722.7	c.3451A>C	p.Asn1151His	missense_variant	15/35	2		ENSP00000374372	P1
SPTB	ENST00000389720.4	c.3451A>C	p.Asn1151His	missense_variant	16/32	5		ENSP00000374370

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 64

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.068
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	17
DANN	Benign	0.64
DEOGEN2	Benign	0.31	.;.;.;T;T
Eigen	Benign	-0.81
Eigen_PC	Benign	-0.68
FATHMM_MKL	Benign	0.31	N
LIST_S2	Benign	0.82	.;.;T;.;T
M_CAP	Benign	0.0054	T
MetaRNN	Benign	0.13	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N;N;N;N;N
MutationTaster	Benign	1.0	P;P;P;P;P
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-1.3	N;.;N;N;N
REVEL	Benign	0.071
Sift	Benign	0.30	T;.;T;T;T
Sift4G	Benign	0.37	T;.;T;T;T
Polyphen		0.0	.;.;.;B;B
Vest4		0.25
MutPred		0.36		Loss of MoRF binding (P = 0.1018);Loss of MoRF binding (P = 0.1018);Loss of MoRF binding (P = 0.1018);Loss of MoRF binding (P = 0.1018);Loss of MoRF binding (P = 0.1018);
MVP		0.32
MPC		0.20
ClinPred		0.19	T
GERP RS		4.9
RBP_binding_hub_radar		1.0
RBP_regulation_power_radar		2.8
Varity_R		0.054
gMVP		0.10

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

Other links and lift over

dbSNP: rs77806; hg19: chr14-65253232;