chr10-97185599-C-G

Position:

• chr10-97185599-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_003061.3(SLIT1):​c.76G>C​(p.Ala26Pro) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: SLIT1 NM_003061.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.375

Genes affected

SLIT1 (HGNC:11085): (slit guidance ligand 1) Enables Roundabout binding activity. Involved in axon extension involved in axon guidance; motor neuron axon guidance; and negative chemotaxis. Predicted to be located in extracellular region. Predicted to be active in extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

ARHGAP19-SLIT1 (HGNC:48348): (ARHGAP19-SLIT1 readthrough (NMD candidate)) This locus represents naturally occurring read-through transcription between the neighboring Rho GTPase activating protein 19 (ARHGAP19) and slit homolog 1 (SLIT1) genes on chromosome 10. The read-through transcript is a candidate for nonsense-mediated mRNA decay (NMD), and is thus unlikely to produce a protein product. [provided by RefSeq, Feb 2011]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.30226493).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLIT1	NM_003061.3	c.76G>C	p.Ala26Pro	missense_variant	1/37	ENST00000266058.9	NP_003052.2
ARHGAP19-SLIT1	NR_037909.1	n.1521-20709G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLIT1	ENST00000266058.9	c.76G>C	p.Ala26Pro	missense_variant	1/37	1	NM_003061.3	ENSP00000266058.4
ARHGAP19-SLIT1	ENST00000479633.2	n.1475-20709G>C		intron_variant		2		ENSP00000473567.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

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

Jan 31, 2023

The c.76G>C (p.A26P) alteration is located in exon 1 (coding exon 1) of the SLIT1 gene. This alteration results from a G to C substitution at nucleotide position 76, causing the alanine (A) at amino acid position 26 to be replaced by a proline (P). 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	Benign	0.16
BayesDel_addAF	Uncertain	0.015	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.053	T;T;T;T
Eigen	Benign	-0.080
Eigen_PC	Benign	-0.057
FATHMM_MKL	Benign	0.37	N
LIST_S2	Benign	0.64	T;T;T;T
M_CAP	Pathogenic	0.33	D
MetaRNN	Benign	0.30	T;T;T;T
MetaSVM	Benign	-0.63	T
MutationAssessor	Benign	0.34	N;.;.;.
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	-1.4	N;N;N;N
REVEL	Uncertain	0.36
Sift	Benign	0.097	T;T;T;T
Sift4G	Benign	0.091	T;T;.;T
Polyphen		0.68	P;.;.;.
Vest4		0.41
MutPred		0.65		Gain of helix (P = 0.0117);Gain of helix (P = 0.0117);.;Gain of helix (P = 0.0117);
MVP		0.59
MPC		0.66
ClinPred		0.25	T
GERP RS		2.7
Varity_R		0.47
gMVP		0.23

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: chr10-98945356;