11-13009737-C-T

Variant names:

• chr11-13009737-C-T
• rs901076428
• NM_001080521.3:c.161C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001080521.3(RASSF10):​c.161C>T​(p.Ser54Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000491 in 1,426,634 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 9/13 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S54W) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000049 (0 hom.)
• Consequence: RASSF10 NM_001080521.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.37
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.030464172).

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.161C>T	p.Ser54Leu	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.161C>T	p.Ser54Leu	missense	Exon 1 of 1	ENSP00000485526.1	A6NK89

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.0000113 AC: 2 AN: 177656 AF XY: 0.0000102

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000153

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000491 AC: 7 AN: 1426634 Hom.: 0 Cov.: 31 AF XY: 0.00000283 AC XY: 2 AN XY: 706394

African (AFR) AF: 0.00 AC: 0 AN: 32630

American (AMR) AF: 0.00 AC: 0 AN: 39242

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25484

East Asian (EAS) AF: 0.0000532 AC: 2 AN: 37586

South Asian (SAS) AF: 0.00 AC: 0 AN: 82312

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48828

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5612

European-Non Finnish (NFE) AF: 0.00000456 AC: 5 AN: 1095864

Other (OTH) AF: 0.00 AC: 0 AN: 59076

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.064
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	4.5
DANN	Benign	0.95
DEOGEN2	Benign	0.0056	T
FATHMM_MKL	Benign	0.051	N
LIST_S2	Benign	0.52	T
MetaRNN	Benign	0.030	T
MutationAssessor	Benign	-0.69	N
PhyloP100		-1.4
PrimateAI	Uncertain	0.68	T
Sift4G	Benign	0.30	T
Polyphen		0.0	B
Vest4		0.071
MVP		0.11
GERP RS		-2.7
PromoterAI		-0.011	Neutral
Varity_R		0.058
gMVP		0.28

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: rs901076428; hg19: chr11-13031284;