14-94306224-C-G

Variant names:

• chr14-94306224-C-G
• rs202038305
• NM_001756.4:c.885-6G>C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001756.4(SERPINA6):​c.885-6G>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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)
• Consequence: SERPINA6 NM_001756.4 splice_region, intron
• Scores: Splicing: ADA: 0.00004615
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.29

Genes affected

SERPINA6 (HGNC:1540): (serpin family A member 6) This gene encodes an alpha-globulin protein with corticosteroid-binding properties. This is the major transport protein for glucorticoids and progestins in the blood of most vertebrates. The gene localizes to a chromosomal region containing several closely related serine protease inhibitors which may have evolved by duplication events. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SERPINA6	NM_001756.4	c.885-6G>C		splice_region_variant, intron_variant	Intron 3 of 4	ENST00000341584.4	NP_001747.3
SERPINA6	XM_047431827.1	c.1056-6G>C		splice_region_variant, intron_variant	Intron 3 of 4		XP_047287783.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SERPINA6	ENST00000341584.4	c.885-6G>C		splice_region_variant, intron_variant	Intron 3 of 4	1	NM_001756.4	ENSP00000342850.3
SERPINA6	ENST00000555056.1	n.*197-6G>C		splice_region_variant, intron_variant	Intron 3 of 4	2		ENSP00000451045.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	11
DANN	Benign	0.38

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000046
SpliceAI score (max)		0.77		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.77		Position offset: -3

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

Publications

LitVar

Other links and lift over

dbSNP: rs202038305; hg19: chr14-94772561;