rs371041609

Variant names:

• chr2-230044-C-A
• rs371041609
• NM_015677.4:c.703G>T

Your query was ambiguous. Multiple possible variants found:

• chr2-230044-C-A
• chr2-230044-C-G
• chr2-230044-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_015677.4(SH3YL1):​c.703G>T​(p.Ala235Ser) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000215 in 1,441,872 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 18/24 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. 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. A235P) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.000021 (0 hom.)
• Consequence: SH3YL1 NM_015677.4 missense, splice_region
• Scores: Splicing: ADA: 0.1549
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.05
• Publications: 2 publications found

Genes affected

SH3YL1 (HGNC:29546): (SH3 and SYLF domain containing 1) Enables phosphatase binding activity and phosphatidylinositol binding activity. Predicted to act upstream of or within phosphatidylinositol biosynthetic process and regulation of ruffle assembly. Located in ruffle membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.095933884).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015677.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SH3YL1	NM_015677.4	MANE Select	c.703G>T	p.Ala235Ser	missense splice_region	Exon 8 of 10	NP_056492.2	Q96HL8-1
	SH3YL1	NM_001159597.3		c.703G>T	p.Ala235Ser	missense splice_region	Exon 8 of 9	NP_001153069.1	Q96HL8-2
	SH3YL1	NM_001282687.2		c.415G>T	p.Ala139Ser	missense splice_region	Exon 10 of 12	NP_001269616.1	Q96HL8-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SH3YL1	ENST00000356150.10	TSL:1 MANE Select	c.703G>T	p.Ala235Ser	missense splice_region	Exon 8 of 10	ENSP00000348471.5	Q96HL8-1
	SH3YL1	ENST00000403712.6	TSL:1	c.703G>T	p.Ala235Ser	missense splice_region	Exon 8 of 9	ENSP00000384276.1	Q96HL8-2
	SH3YL1	ENST00000626873.2	TSL:5	c.415G>T	p.Ala139Ser	missense splice_region	Exon 11 of 13	ENSP00000485824.1	Q96HL8-3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000838 AC: 2 AN: 238680 AF XY: 0.00000773

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000181

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000215 AC: 31 AN: 1441872 Hom.: 0 Cov.: 29 AF XY: 0.0000265 AC XY: 19 AN XY: 716028

African (AFR) AF: 0.00 AC: 0 AN: 32670

American (AMR) AF: 0.00 AC: 0 AN: 41950

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25452

East Asian (EAS) AF: 0.00 AC: 0 AN: 39408

South Asian (SAS) AF: 0.00 AC: 0 AN: 82706

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53040

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5662

European-Non Finnish (NFE) AF: 0.0000272 AC: 30 AN: 1101470

Other (OTH) AF: 0.0000168 AC: 1 AN: 59514

GnomAD4 genome Cov.: 33

Alfa AF: 0.000142 Hom.: 0

Bravo AF: 0.00000378

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000122 AC: 1

ExAC AF: 0.00000828 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.073
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	15
DANN	Benign	0.27
DEOGEN2	Benign	0.060	T
Eigen	Benign	-0.53
Eigen_PC	Benign	-0.36
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.66	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.096	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.4	L
PhyloP100		1.0
PrimateAI	Benign	0.32	T
PROVEAN	Benign	0.27	N
REVEL	Benign	0.11
Sift	Benign	0.69	T
Sift4G	Benign	0.81	T
Polyphen		0.0060	B
Vest4		0.24
MVP		0.18
MPC		0.073
ClinPred		0.091	T
GERP RS		4.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.057
gMVP		0.44
Mutation Taster		=76/24	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.15
dbscSNV1_RF	Benign	0.47
SpliceAI score (max)		0.14		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs371041609; hg19: chr2-230044;