chr14-61767312-G-T

Variant names:

• chr14-61767312-G-T
• rs779670803
• NM_003082.4:c.389G>T

Variant summary

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

The NM_003082.4(SNAPC1):​c.389G>T​(p.Arg130Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000146 in 1,366,580 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R130Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000015 (0 hom.)
• Consequence: SNAPC1 NM_003082.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.03
• Publications: 0 publications found

Genes affected

SNAPC1 (HGNC:11134): (small nuclear RNA activating complex polypeptide 1) Predicted to enable sequence-specific DNA binding activity. Predicted to be involved in snRNA transcription by RNA polymerase II and snRNA transcription by RNA polymerase III. Located in nucleolus and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000258964 (HGNC:):

ACMG classification

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

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003082.4. 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
	SNAPC1	NM_003082.4	MANE Select	c.389G>T	p.Arg130Leu	missense	Exon 3 of 10	NP_003073.1	Q16533

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SNAPC1	ENST00000216294.5	TSL:1 MANE Select	c.389G>T	p.Arg130Leu	missense	Exon 3 of 10	ENSP00000216294.4	Q16533
	SNAPC1	ENST00000923634.1		c.389G>T	p.Arg130Leu	missense	Exon 3 of 11	ENSP00000593693.1
	SNAPC1	ENST00000923637.1		c.389G>T	p.Arg130Leu	missense	Exon 3 of 11	ENSP00000593696.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000146 AC: 2 AN: 1366580 Hom.: 0 Cov.: 29 AF XY: 0.00000148 AC XY: 1 AN XY: 676190

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 28804

American (AMR) AF: 0.00 AC: 0 AN: 31376

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23292

East Asian (EAS) AF: 0.00 AC: 0 AN: 35760

South Asian (SAS) AF: 0.0000285 AC: 2 AN: 70156

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5428

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1065428

Other (OTH) AF: 0.00 AC: 0 AN: 55718

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.33
BayesDel_addAF	Uncertain	0.034	T
BayesDel_noAF	Benign	-0.19
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0099	T
Eigen	Uncertain	0.37
Eigen_PC	Uncertain	0.48
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.0038	T
MetaRNN	Uncertain	0.53	D
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	2.0	M
PhyloP100		5.0
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.24
Sift	Benign	0.83	T
Sift4G	Benign	1.0	T
Polyphen		0.90	P
Vest4		0.55
MutPred		0.56		Gain of catalytic residue at K128 (P = 0)
MVP		0.27
MPC		0.31
ClinPred		0.95	D
GERP RS		5.9
Varity_R		0.18
gMVP		0.49
Mutation Taster		=64/36	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs779670803; hg19: chr14-62234030;