6-70755016-C-T

Position:

• chr6-70755016-C-T

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4 BS2

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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.06

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]

ACMG classification

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
SMAP1	NM_001044305.3	c.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
SMAP1	ENST00000370455.8	c.289C>T	p.Leu97Phe	missense_variant	3/11	1	NM_001044305.3	ENSP00000359484	P3
SMAP1	ENST00000619054.4	c.259C>T	p.Leu87Phe	missense_variant	3/11	1		ENSP00000484538
SMAP1	ENST00000316999.9	c.289C>T	p.Leu97Phe	missense_variant	3/10	1		ENSP00000313382	A1
SMAP1	ENST00000370452.7	c.289C>T	p.Leu97Phe	missense_variant	3/11	2		ENSP00000359481

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

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

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 29, 2024

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	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;