11-13009962-T-C

Variant names:

• chr11-13009962-T-C
• rs371219653
• NM_001080521.3:c.386T>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 3P and 1B. PM2 PP3 BP4

The NM_001080521.3(RASSF10):​c.386T>C​(p.Val129Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000706 in 1,416,188 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 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. V129G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: RASSF10 NM_001080521.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.89
• Publications: 0 publications found

Genes affected

RASSF10 (HGNC:33984): (Ras association domain family member 10) Predicted to be involved in positive regulation of neural precursor cell proliferation and positive regulation of neurogenesis. Predicted to be located in cytosol; microtubule organizing center; and spindle pole. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: Multiple lines of computational evidence support a deleterious effect 5: AlphaMissense, BayesDel_addAF, Cadd, phyloP100way_vertebrate, PrimateAI [when Dann, max_spliceai, MetaRNN was below the threshold]
• BP4: Computational evidence support a benign effect (MetaRNN=0.3637739).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001080521.3. 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
	RASSF10	NM_001080521.3	MANE Select	c.386T>C	p.Val129Ala	missense	Exon 1 of 1	NP_001073990.2	A6NK89

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RASSF10	ENST00000529419.3	TSL:6 MANE Select	c.386T>C	p.Val129Ala	missense	Exon 1 of 1	ENSP00000485526.1	A6NK89

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00 AC: 0 AN: 175354 AF XY: 0.00

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 7.06e-7 AC: 1 AN: 1416188 Hom.: 0 Cov.: 32 AF XY: 0.00000143 AC XY: 1 AN XY: 699856

African (AFR) AF: 0.00 AC: 0 AN: 32526

American (AMR) AF: 0.00 AC: 0 AN: 38406

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25374

East Asian (EAS) AF: 0.00 AC: 0 AN: 37314

South Asian (SAS) AF: 0.00 AC: 0 AN: 81040

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49020

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5708

European-Non Finnish (NFE) AF: 9.19e-7 AC: 1 AN: 1088226

Other (OTH) AF: 0.00 AC: 0 AN: 58574

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.92
BayesDel_addAF	Pathogenic	0.21	D
BayesDel_noAF	Uncertain	0.070
CADD	Pathogenic	26
DANN	Benign	0.92
DEOGEN2	Benign	0.11	T
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.85	D
MetaRNN	Benign	0.36	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		7.9
PrimateAI	Pathogenic	0.88	D
Sift4G	Uncertain	0.0060	D
Polyphen		0.037	B
Vest4		0.66
MVP		0.076
GERP RS		4.7
Varity_R		0.21
gMVP		0.56

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

Other links and lift over

dbSNP: rs371219653; hg19: chr11-13031509;