6-166329522-A-G

Variant names:

• chr6-166329522-A-G
• rs1030666518
• NM_145169.3:c.218T>C

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_145169.3(SFT2D1):​c.218T>C​(p.Leu73Pro) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,456,924 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: SFT2D1 NM_145169.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.93
• Publications: 0 publications found

Genes affected

SFT2D1 (HGNC:21102): (SFT2 domain containing 1) Predicted to be involved in protein transport and vesicle-mediated transport. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.852

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145169.3. 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
	SFT2D1	NM_145169.3	MANE Select	c.218T>C	p.Leu73Pro	missense	Exon 3 of 8	NP_660152.1	Q8WV19
	SFT2D1	NR_130112.2		n.305T>C		non_coding_transcript_exon	Exon 4 of 9
	SFT2D1	NR_130113.2		n.305T>C		non_coding_transcript_exon	Exon 4 of 7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SFT2D1	ENST00000361731.4	TSL:1 MANE Select	c.218T>C	p.Leu73Pro	missense	Exon 3 of 8	ENSP00000354590.3	Q8WV19
	SFT2D1	ENST00000487841.5	TSL:1	n.307T>C		non_coding_transcript_exon	Exon 4 of 8
	SFT2D1	ENST00000921768.1		c.218T>C	p.Leu73Pro	missense	Exon 3 of 8	ENSP00000591827.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1456924 Hom.: 0 Cov.: 30 AF XY: 0.00000276 AC XY: 2 AN XY: 724798

African (AFR) AF: 0.00 AC: 0 AN: 33428

American (AMR) AF: 0.00 AC: 0 AN: 44634

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26020

East Asian (EAS) AF: 0.00 AC: 0 AN: 39674

South Asian (SAS) AF: 0.00 AC: 0 AN: 85478

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53190

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5754

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1108618

Other (OTH) AF: 0.00 AC: 0 AN: 60128

GnomAD4 genome Cov.: 33

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	Pathogenic	0.91
BayesDel_addAF	Uncertain	0.095	D
BayesDel_noAF	Benign	-0.10
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.23	T
Eigen	Uncertain	0.23
Eigen_PC	Uncertain	0.23
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.019	T
MetaRNN	Pathogenic	0.85	D
MetaSVM	Benign	-0.65	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		6.9
PrimateAI	Uncertain	0.61	T
PROVEAN	Pathogenic	-4.7	D
REVEL	Uncertain	0.45
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0020	D
Polyphen		0.29	B
Vest4		0.88
MutPred		0.73		Loss of helix (P = 3e-04)
MVP		0.41
MPC		0.73
ClinPred		1.0	D
GERP RS		4.9
Varity_R		0.93
gMVP		0.93
Mutation Taster		=28/72	disease causing

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

Other links and lift over

dbSNP: rs1030666518; hg19: chr6-166743010;