chr6-70755016-C-T

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_001044305.3(SMAP1):​c.289C>T​(p.Leu97Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000891 in 1,458,394 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000089 ( 0 hom. )

Consequence

SMAP1
NM_001044305.3 missense

Scores

1
6
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.06
Variant links:
Genes affected
SMAP1 (HGNC:19651): (small ArfGAP 1) The protein encoded by this gene is similar to the mouse stromal membrane-associated protein-1. This similarity suggests that this human gene product is also a type II membrane glycoprotein involved in the erythropoietic stimulatory activity of stromal cells. Alternate splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.33883902).
BS2
High AC in GnomAdExome4 at 13 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SMAP1NM_001044305.3 linkuse as main transcriptc.289C>T p.Leu97Phe missense_variant 3/11 ENST00000370455.8 NP_001037770.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SMAP1ENST00000370455.8 linkuse as main transcriptc.289C>T p.Leu97Phe missense_variant 3/111 NM_001044305.3 ENSP00000359484 P3Q8IYB5-1
SMAP1ENST00000619054.4 linkuse as main transcriptc.259C>T p.Leu87Phe missense_variant 3/111 ENSP00000484538
SMAP1ENST00000316999.9 linkuse as main transcriptc.289C>T p.Leu97Phe missense_variant 3/101 ENSP00000313382 A1Q8IYB5-2
SMAP1ENST00000370452.7 linkuse as main transcriptc.289C>T p.Leu97Phe missense_variant 3/112 ENSP00000359481 Q8IYB5-3

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000891
AC:
13
AN:
1458394
Hom.:
0
Cov.:
30
AF XY:
0.00000827
AC XY:
6
AN XY:
725514
show subpopulations
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:
0.0000117
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsMay 29, 2024The c.289C>T (p.L97F) alteration is located in exon 3 (coding exon 3) of the SMAP1 gene. This alteration results from a C to T substitution at nucleotide position 289, causing the leucine (L) at amino acid position 97 to be replaced by a phenylalanine (F). 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
Uncertain
0.45
BayesDel_addAF
Benign
-0.12
T
BayesDel_noAF
Benign
-0.41
CADD
Uncertain
24
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.14
.;.;T;.
Eigen
Benign
0.044
Eigen_PC
Benign
0.20
FATHMM_MKL
Uncertain
0.90
D
LIST_S2
Uncertain
0.95
D;D;D;D
M_CAP
Benign
0.011
T
MetaRNN
Benign
0.34
T;T;T;T
MetaSVM
Benign
-0.97
T
MutationAssessor
Benign
0.050
N;N;N;.
MutationTaster
Benign
1.0
D;D;D;D
PrimateAI
Uncertain
0.59
T
PROVEAN
Uncertain
-2.9
D;D;D;.
REVEL
Benign
0.097
Sift
Benign
0.061
T;T;T;.
Sift4G
Uncertain
0.053
T;T;T;D
Polyphen
0.068
B;B;D;.
Vest4
0.41
MutPred
0.48
Gain of helix (P = 0.132);Gain of helix (P = 0.132);Gain of helix (P = 0.132);.;
MVP
0.16
MPC
0.60
ClinPred
0.96
D
GERP RS
5.0
Varity_R
0.28
gMVP
0.78

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: chr6-71464719; API