17-77216831-T-A

Variant names:

• chr17-77216831-T-A
• rs12263
• NM_001143998.2:c.*2808T>A

Variant summary

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

The NM_001143998.2(SEC14L1):​c.*2808T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000266 in 375,296 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.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: SEC14L1 NM_001143998.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.116
• Publications: 0 publications found

Genes affected

SEC14L1 (HGNC:10698): (SEC14 like lipid binding 1) The protein encoded by this gene belongs to the SEC14 cytosolic factor family. It has similarity to yeast SEC14 and to Japanese flying squid RALBP which suggests a possible role of the gene product in an intracellular transport system. Multiple alternatively spliced transcript variants have been found for this gene; some variants represent read-through transcripts that include exons from the upstream gene C17orf86. [provided by RefSeq, Feb 2011]

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 (BayesDel_noAF=-0.79).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001143998.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEC14L1	NM_001143998.2	MANE Select	c.*2808T>A		3_prime_UTR	Exon 17 of 17	NP_001137470.2
	SEC14L1	NM_001039573.3		c.*267T>A		3_prime_UTR	Exon 18 of 18	NP_001034662.3
	SEC14L1	NM_001204408.2		c.*267T>A		3_prime_UTR	Exon 20 of 20	NP_001191337.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEC14L1	ENST00000436233.9	TSL:1 MANE Select	c.*2808T>A		3_prime_UTR	Exon 17 of 17	ENSP00000390392.3
	SEC14L1	ENST00000443798.8	TSL:1	c.*267T>A		3_prime_UTR	Exon 18 of 18	ENSP00000406030.3
	SEC14L1	ENST00000392476.6	TSL:2	c.*267T>A		downstream_gene	N/A	ENSP00000376268.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000266 AC: 1 AN: 375296 Hom.: 0 Cov.: 5 AF XY: 0.00000509 AC XY: 1 AN XY: 196604

⚠️ 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: 10870

American (AMR) AF: 0.00 AC: 0 AN: 11812

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 10982

East Asian (EAS) AF: 0.00 AC: 0 AN: 23426

South Asian (SAS) AF: 0.00 AC: 0 AN: 37404

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 22348

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1576

European-Non Finnish (NFE) AF: 0.00000424 AC: 1 AN: 235960

Other (OTH) AF: 0.00 AC: 0 AN: 20918

⚠️ 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.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	1.3
DANN	Benign	0.60
PhyloP100		-0.12
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

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

Other links and lift over

dbSNP: rs12263; hg19: chr17-75212913;