chr6-166320236-C-T

Variant names:

• chr6-166320236-C-T
• rs1223752762
• NM_145169.3:c.461G>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_145169.3(SFT2D1):​c.461G>A​(p.Cys154Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000343 in 1,459,366 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: SFT2D1 NM_145169.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.878

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1887115).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SFT2D1	NM_145169.3	c.461G>A	p.Cys154Tyr	missense_variant	Exon 8 of 8	ENST00000361731.4	NP_660152.1
SFT2D1	NR_130112.2	n.548G>A		non_coding_transcript_exon_variant	Exon 9 of 9
SFT2D1	NR_130113.2	n.453G>A		non_coding_transcript_exon_variant	Exon 7 of 7
SFT2D1	NR_130114.2	n.444G>A		non_coding_transcript_exon_variant	Exon 7 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SFT2D1	ENST00000361731.4	c.461G>A	p.Cys154Tyr	missense_variant	Exon 8 of 8	1	NM_145169.3	ENSP00000354590.3
SFT2D1	ENST00000479490.1	n.1853G>A		non_coding_transcript_exon_variant	Exon 2 of 2	1
SFT2D1	ENST00000487841.5	n.2200G>A		non_coding_transcript_exon_variant	Exon 8 of 8	1
SFT2D1	ENST00000478705.5	n.579G>A		non_coding_transcript_exon_variant	Exon 9 of 9	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000343 AC: 5 AN: 1459366 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 725918

Gnomad4 AFR exome AF: 0.0000300

Gnomad4 AMR exome AF: 0.0000226

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000270

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 05, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.461G>A (p.C154Y) alteration is located in exon 8 (coding exon 8) of the SFT2D1 gene. This alteration results from a G to A substitution at nucleotide position 461, causing the cysteine (C) at amino acid position 154 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.44
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	22
DANN	Benign	0.61
DEOGEN2	Benign	0.018	T
Eigen	Benign	-0.24
Eigen_PC	Benign	-0.23
FATHMM_MKL	Benign	0.71	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.0065	T
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Uncertain	2.5	M
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	0.39	N
REVEL	Benign	0.14
Sift	Benign	0.030	D
Sift4G	Benign	0.075	T
Polyphen		0.52	P
Vest4		0.50
MutPred		0.42		Gain of disorder (P = 0.0666);
MVP		0.076
MPC		0.60
ClinPred		0.76	D
GERP RS		3.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.13
gMVP		0.81

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs1223752762; hg19: chr6-166733724;