chr14-61768648-A-T

Variant names:

• chr14-61768648-A-T
• rs1206965019
• NM_003082.4:c.442A>T

Variant summary

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

The NM_003082.4(SNAPC1):​c.442A>T​(p.Met148Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000314 in 1,591,400 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000028 (0 hom.)
• Consequence: SNAPC1 NM_003082.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.49
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12617823).

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.442A>T	p.Met148Leu	missense	Exon 4 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.442A>T	p.Met148Leu	missense	Exon 4 of 10	ENSP00000216294.4	Q16533
	SNAPC1	ENST00000923634.1		c.442A>T	p.Met148Leu	missense	Exon 4 of 11	ENSP00000593693.1
	SNAPC1	ENST00000923637.1		c.442A>T	p.Met148Leu	missense	Exon 4 of 11	ENSP00000593696.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152232 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000278 AC: 4 AN: 1439168 Hom.: 0 Cov.: 27 AF XY: 0.00000139 AC XY: 1 AN XY: 717670

African (AFR) AF: 0.00 AC: 0 AN: 32980

American (AMR) AF: 0.00 AC: 0 AN: 44534

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25946

East Asian (EAS) AF: 0.00 AC: 0 AN: 39514

South Asian (SAS) AF: 0.00 AC: 0 AN: 85686

European-Finnish (FIN) AF: 0.0000189 AC: 1 AN: 53032

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5728

European-Non Finnish (NFE) AF: 0.00000275 AC: 3 AN: 1092154

Other (OTH) AF: 0.00 AC: 0 AN: 59594

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152232 Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1 AN XY: 74380

African (AFR) AF: 0.00 AC: 0 AN: 41462

American (AMR) AF: 0.00 AC: 0 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5200

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.0000941 AC: 1 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68034

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

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	0.15
BayesDel_addAF	Benign	-0.036	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	21
DANN	Benign	0.85
DEOGEN2	Benign	0.016	T
Eigen	Benign	-0.21
Eigen_PC	Benign	-0.049
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.0035	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	L
PhyloP100		4.5
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-0.91	N
REVEL	Benign	0.036
Sift	Benign	0.59	T
Sift4G	Benign	0.54	T
Polyphen		0.17	B
Vest4		0.30
MutPred		0.42		Gain of catalytic residue at L144 (P = 0.0153)
MVP		0.12
MPC		0.087
ClinPred		0.78	D
GERP RS		4.4
Varity_R		0.079
gMVP		0.25
Mutation Taster		=94/6	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs1206965019; hg19: chr14-62235366;