17-77191242-C-G

Position:

• chr17-77191242-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP2

The NM_001143998.2(SEC14L1):​c.275C>G​(p.Thr92Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SEC14L1 NM_001143998.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.47

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

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant where missense usually causes diseases, SEC14L1

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SEC14L1	NM_001143998.2	c.275C>G	p.Thr92Ser	missense_variant	5/17	ENST00000436233.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SEC14L1	ENST00000436233.9	c.275C>G	p.Thr92Ser	missense_variant	5/17	1	NM_001143998.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Uncertain	0.056	T
BayesDel_noAF	Benign	-0.16
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.018	T;.;T;T;T;.;.;T;.;T
Eigen	Uncertain	0.33
Eigen_PC	Uncertain	0.41
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.79	T;.;.;.;T;T;.;T;T;T
M_CAP	Benign	0.019	T
MetaRNN	Uncertain	0.59	D;D;D;D;D;D;D;D;D;D
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	1.0	D;D;D;D;D;D;D;D
PrimateAI	Uncertain	0.69	T
Sift4G	Benign	0.11	T;T;T;T;T;T;T;T;T;D
Polyphen		0.32, 0.38	.;B;B;B;B;B;.;.;.;.
Vest4		0.67, 0.67, 0.67, 0.67, 0.67, 0.66
MutPred		0.48		Gain of disorder (P = 0.0294);Gain of disorder (P = 0.0294);Gain of disorder (P = 0.0294);Gain of disorder (P = 0.0294);Gain of disorder (P = 0.0294);Gain of disorder (P = 0.0294);.;.;.;.;
MVP		0.46
MPC		1.1
ClinPred		0.98	D
GERP RS		5.0
Varity_R		0.34
gMVP		0.49

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-75187324;