Genetic Variant SMAP1:p.Leu97Phe (chr6-70755016-C-T) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -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

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.06

Publications

0 publications found

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]

SMAP1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -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 rank	MANE	Protein	UniProt
SMAP1	NM_001044305.3 link	c.289C>T	p.Leu97Phe	missense_variant	Exon 3 of 11	ENST00000370455.8	NP_001037770.1	Q8IYB5-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SMAP1	ENST00000370455.8 link	c.289C>T	p.Leu97Phe	missense_variant	Exon 3 of 11	1	NM_001044305.3	ENSP00000359484.3	Q8IYB5-1
SMAP1	ENST00000619054.4 link	c.259C>T	p.Leu87Phe	missense_variant	Exon 3 of 11	1		ENSP00000484538.1	A0A087X1X9
SMAP1	ENST00000316999.9 link	c.289C>T	p.Leu97Phe	missense_variant	Exon 3 of 10	1		ENSP00000313382.5	Q8IYB5-2
SMAP1	ENST00000370452.7 link	c.289C>T	p.Leu97Phe	missense_variant	Exon 3 of 11	2		ENSP00000359481.3	Q8IYB5-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000891

AC:

AN:

1458394

Hom.:

Cov.:

AF XY:

0.00000827

AC XY:

AN XY:

725514

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33362

American (AMR)

AF:

0.00

AC:

AN:

44664

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26002

East Asian (EAS)

AF:

0.00

AC:

AN:

39524

South Asian (SAS)

AF:

0.00

AC:

AN:

86004

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53310

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5734

European-Non Finnish (NFE)

AF:

0.0000117

AC:

AN:

1109606

Other (OTH)

AF:

0.00

AC:

AN:

60188

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

May 29, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The 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

BayesDel_noAF

Benign

-0.41

CADD

Uncertain

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.14

.;.;T;.

Eigen

Benign

0.044

Eigen_PC

Benign

0.20

FATHMM_MKL

Uncertain

0.90

LIST_S2

Uncertain

0.95

D;D;D;D

M_CAP

Benign

0.011

MetaRNN

Benign

0.34

T;T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.050

N;N;N;.

PhyloP100

3.1

PrimateAI

Uncertain

0.59

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

GERP RS

5.0

Varity_R

0.28

gMVP

0.78

Mutation Taster

=26/74

disease causing

(source)

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

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6-70755016-C-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over